TON May 2015 Vol 8 No 3

MAY 2015

www.TheOncologyNurse.com

Managing Dermatologic Toxicities

CANCER CENTER PROFILE

Taussig Cancer Institute

Audrey Andrews

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The staff at the Taussig CAT clinic (left to right): Meghan O’Brien, MSN, CNP; Kristine Adams, MSN, CNP; and Kimberly Hamilton, MSN, CNP. Not pictured are Beth Faiman, PhD, APRN-BC, AOCN, and Vicki Pinkava, PA-C.

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he Taussig Cancer Institute, part of the Cleveland Clinic, is one of the National Cancer Institute’s designated comprehensive cancer centers in the United States, offering care for patients with all types of cancer.

Each year, more than 250 doctors, nurses, and other healthcare professionals provide advanced cancer care to more than 14,000 patients with cancer.

Continued on page 6

CONFERENCE NEWS

Highlights From the 2015 Genitourinary Cancers Symposium

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pproximately 3000 oncology experts gathered to hear about the latest advances in treating prostate, bladder, testicular, kidney, and penile cancers at the 2015 Genitourinary Cancers Symposium, held February 26-28, 2015, in Orlando, Florida. The symposium, cosponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology, explored the theme of “integrating biology into patient-centric care.” Below are news summaries of presentations of interest to nurses and advanced nurse practitioners.

Abiraterone and Metabolic Syndrome

Abiraterone is a highly effective and widely used drug in men with metastatic castration-resistant prostate cancer (CRPC). A preliminary study suggests that abiraterone may increase the risk of developing metabolic syndrome, and that the presence of metabolic syn-

VOL 8, NO 3

drome is a significant risk factor for shorter progression-free survival in men with metastatic CRPC treated with abiraterone. No significant effect of metabolic syndrome was observed on overall survival in men with CRPC treated with abiraterone.

Continued on page 13

ncology nurses are tasked with helping patients with cancer manage the toxicities of their treatment. With the advent of targeted therapies, this challenge has become greater. At the National Comprehensive Cancer Network (NCCN) 20th Annual Conference, Mario E. Lacouture, MD, one of the foremost experts in dermatologic toxicities, presented some clinical pearls that can guide management of these toxicities.1 Lacouture is Associate Professor of Dermatology at Cornell University and Associate Member of Memorial Sloan Kettering Cancer Center, New York.

Skin Rash and Related Symptoms

Therapeutic targeting of the epidermal growth factor receptor (EGFR) commonly produces skin rash (Figure 1), but other agents—including BRAF, mTOR, and immune checkpoint inhibitors—can also produce rash, as can some older agents, such as liposomal doxorubicin and gemcitabine. Lacouture made these recommendations for managing rash: • Mainstay of treatment for most rashes is topical corticosteroids; in higher grades of rash, oral corticosteroids and antibiotics may be warranted.

Continued on page 7

Inherited Ovarian Cancer: What Have We Learned?

Cristi Radford, MS, CGC

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ompared with other cancers, ovarian cancer is relatively rare, accounting for just 1.3% of all new cancer cases in the United States.

However, it has a high death rate—the highest of any female reproductive system cancer. Only around 1 in 7 women with ovarian cancer are diagnosed at the local stage. For these women, the 5-year survival is optimistic at 92%. However, most women present with advanced disease, for which the overall 5-year survival is estimated to be 45%.1 The

INSIDE 3 Prostate Cancer Stereotactic Body Radiation Therapy Shows Acceptable Urinary and Sexual Toxicity AR-V7 Predicts Chemotherapy Sensitivity in Metastatic Prostate Cancer 8 Best Practices Maximizing Efficacy in the Infusion Unit: Making Patients and Nurses Happy

© 2015 Green Hill Healthcare Communications, LLC

low survival rate is primarily due to the inability to detect ovarian cancer at an early, curable stage. Whereas the average woman has approximately a 1.5% chance of developing ovarian cancer in her lifetime, a high-risk woman with a BRCA mutation may have anywhere from a 15% to a 68% lifetime risk.2 Screening options for ovarian cancer are extremely limited, and, to date, there are no proven effective surveillance strategies. Both the US Preventive Services Task Force and the American Continued on page 15

New NCCN Guideline Addresses Smoking Cessation in Patients With Cancer 17 Nutrition in Focus

Helping a Loved One With Cancer Eat Better During Treatment and Adjusting to Life and Nutrition After Treatment 18 Navigation

What Is a Navigator?

Take a bite out of G-CSF acquisition costs Based on wholesale acquisition cost (WAC) of all short-acting G-CSF products as of November 11, 2013. WAC represents published catalogue or list prices and may not represent actual transactional prices. Please contact your supplier for actual prices.

GRANIX® is an option in short-acting G-CSF therapy » A 71% reduction in duration of severe neutropenia vs placebo (1.1 days vs 3.8 days, p<0.0001)1 – Efficacy was evaluated in a multinational, multicenter, randomized, controlled, Phase III study of chemotherapy-naïve patients with high-risk breast cancer receiving doxorubicin (60 mg/m2 IV bolus)/docetaxel (75 mg/m2)1 » The safety of GRANIX was established in 3 Phase III trials, with 680 patients receiving chemotherapy for either breast cancer, lung cancer, or non-Hodgkin lymphoma (NHL)1 » Now offering a new presentation for self-administration

Indication » GRANIX is a leukocyte growth factor indicated for reduction in the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.

Important Safety Information » Splenic rupture: Splenic rupture, including fatal cases, can occur following the administration of human granulocyte colony-stimulating factors (hG-CSFs). Discontinue GRANIX and evaluate for an enlarged spleen or splenic rupture in patients who report upper abdominal or shoulder pain after receiving GRANIX. » Acute respiratory distress syndrome (ARDS): ARDS can occur in patients receiving hG-CSFs. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients with ARDS. » Allergic reactions: Serious allergic reactions, including anaphylaxis, can occur in patients receiving hG-CSFs. Reactions can occur on initial exposure. Permanently discontinue GRANIX in patients with serious allergic reactions. Do not administer GRANIX to patients with a history of serious allergic reactions to filgrastim or pegfilgrastim. » Use in patients with sickle cell disease: Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disease receiving hG-CSFs. Consider the potential risks and benefits prior to the administration of GRANIX in patients with sickle cell disease. Discontinue GRANIX in patients undergoing a sickle cell crisis. » Capillary leak syndrome (CLS): CLS can occur in patients receiving hG-CSFs and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of CLS should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care. » Potential for tumor growth stimulatory effects on malignant cells: The granulocyte colony-stimulating factor (G-CSF) receptor, through which GRANIX acts, has been found on tumor cell lines. The possibility that GRANIX acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which GRANIX is not approved, cannot be excluded. » Most common treatment-emergent adverse reaction: The most common treatment-emergent adverse reaction that occurred in patients treated with GRANIX at the recommended dose with an incidence of at least 1% or greater and two times more frequent than in the placebo group was bone pain.

Please see brief summary of Full Prescribing Information on adjacent page.

For more information, visit GRANIXhcp.com.

Reference: 1. GRANIX® (tbo-filgrastim) Injection Prescribing Information. North Wales, PA: Teva Pharmaceuticals; 2014.

©2015 Cephalon, Inc., a wholly-owned subsidiary of Teva Pharmaceutical Industries Ltd. GRANIX is a registered trademark of Teva Pharmaceutical Industries Ltd. All rights reserved. GRX-40582 January 2015.

PROSTATE CANCER

Stereotactic Body Radiation Therapy Shows Acceptable Urinary and Sexual Toxicity Chase Doyle

A

lthough recent studies have shown the efficacy of using ster­ eotactic body radiation therapy (SBRT) as a treatment modality for organ-confined prostate cancer, questions over urinary symptoms and sexual dysfunction have remained. According

to findings presented at the 2015 Genitourinary Cancers Symposium, those questions have been answered: the SBRT approach demonstrates acceptable urinary and sexual toxicity.

“While an increase in IPSS [International Prostate Symptom Score] irrita-

BRIEF SUMMARY OF PRESCRIBING INFORMATION FOR GRANIX® (tbo-filgrastim) injection, for subcutaneous use SEE PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE GRANIX is indicated to reduce the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

4 CONTRAINDICATIONS None.

5 WARNINGS AND PRECAUTIONS 5.1 Splenic Rupture Splenic rupture, including fatal cases, can occur following administration of human granulocyte colony-stimulating factors. In patients who report upper abdominal or shoulder pain after receiving GRANIX, discontinue GRANIX and evaluate for an enlarged spleen or splenic rupture.

5.2 Acute Respiratory Distress Syndrome (ARDS) Acute respiratory distress syndrome (ARDS) can occur in patients receiving human granulocyte colony-stimulating factors. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients with ARDS. 5.3 Allergic Reactions Serious allergic reactions including anaphylaxis can occur in patients receiving human granulocyte colony-stimulating factors. Reactions can occur on initial exposure. The administration of antihistamines‚ steroids‚ bronchodilators‚ and/or epinephrine may reduce the severity of the reactions. Permanently discontinue GRANIX in patients with serious allergic reactions. Do not administer GRANIX to patients with a history of serious allergic reactions to filgrastim or pegfilgrastim.

5.4 Use in Patients with Sickle Cell Disease Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disease receiving human granulocyte colony-stimulating factors. Consider the potential risks and benefits prior to the administration of human granulocyte colony-stimulating factors in patients with sickle cell disease. Discontinue GRANIX in patients undergoing a sickle cell crisis.

5.5 Capillary Leak Syndrome Capillary leak syndrome (CLS) can occur in patients receiving human granulocyte colonystimulating factors and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care.

5.6 Potential for Tumor Growth Stimulatory Effects on Malignant Cells The granulocyte colony-stimulating factor (G-CSF) receptor through which GRANIX acts has been found on tumor cell lines. The possibility that GRANIX acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which GRANIX is not approved, cannot be excluded.

6 ADVERSE REACTIONS The following potential serious adverse reactions are discussed in greater detail in other sections of the labeling: • Splenic Rupture [see Warnings and Precautions (5.1)] • Acute Respiratory Distress Syndrome [see Warnings and Precautions (5.2)] • Serious Allergic Reactions [see Warnings and Precautions (5.3)] • Use in Patients with Sickle Cell Disease [see Warnings and Precautions (5.4)] • Capillary Leak Syndrome [see Warnings and Precautions (5.5)] • Potential for Tumor Growth Stimulatory Effects on Malignant Cells [see Warnings and Precautions (5.6)] The most common treatment-emergent adverse reaction that occurred at an incidence of at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo group was bone pain.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

GRANIX clinical trials safety data are based upon the results of three randomized clinical trials in patients receiving myeloablative chemotherapy for breast cancer (N=348), lung cancer (N=240) and non-Hodgkin’s lymphoma (N=92). In the breast cancer study, 99% of patients were female, the median age was 50 years, and 86% of patients were Caucasian.

In the lung cancer study, 80% of patients were male, the median age was 58 years, and 95% of patients were Caucasian. In the non-Hodgkin’s lymphoma study, 52% of patients were male, the median age was 55 years, and 88% of patients were Caucasian. In all three studies a placebo (Cycle 1 of the breast cancer study only) or a non-US-approved filgrastim product were used as controls. Both GRANIX and the non-US-approved filgrastim product were administered at 5 mcg/kg subcutaneously once daily beginning one day after chemotherapy for at least five days and continued to a maximum of 14 days or until an ANC of ≥10,000 x 106/L after nadir was reached.

tive score and a decrease in SHIM [Sexual Health Inventory for Men] score initially occurred, all symptoms return to baseline within 3 years,” said Zaker H. Rana, MD, Department of Radiation Oncology, Virginia Hospital Center, Arlington. “Age did not affect

Bone pain was the most frequent treatment-emergent adverse reaction that occurred in at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo group. The overall incidence of bone pain in Cycle 1 of treatment was 3.4% (3.4% GRANIX, 1.4% placebo, 7.5% non-USapproved filgrastim product).

Leukocytosis In clinical studies, leukocytosis (WBC counts > 100,000 x 106/L) was observed in less than 1% patients with non-myeloid malignancies receiving GRANIX. No complications attributable to leukocytosis were reported in clinical studies.

Additional Adverse Reactions Other adverse reactions known to occur following administration of human granulocyte colony-stimulating factors include myalgia, headache, vomiting, Sweet’s syndrome (acute febrile neutrophilic dermatosis), cutaneous vasculitis and thrombocytopenia.

6.2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The incidence of antibody development in patients receiving GRANIX has not been adequately determined.

7 DRUG INTERACTIONS No formal drug interaction studies between GRANIX and other drugs have been performed.

Drugs which may potentiate the release of neutrophils‚ such as lithium‚ should be used with caution.

Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C Risk Summary There are no adequate and well-controlled studies of GRANIX in pregnant women. In animal reproduction studies, treatment of pregnant rabbits with tbo-filgrastim resulted in increased spontaneous abortion and fetal malformations at systemic exposures substantially higher than the human exposure. GRANIX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Animal Data In an embryofetal developmental study, pregnant rabbits were administered subcutaneous doses of tbo-filgrastim during the period of organogenesis at 1, 10 and 100 mcg/kg/day.

Increased abortions were evident in rabbits treated with tbo-filgrastim at 100 mcg/kg/day.

This dose was maternally toxic as demonstrated by reduced body weight. Other embryofetal findings at this dose level consisted of post-implantation loss‚ decrease in mean live litter size and fetal weight, and fetal malformations such as malformed hindlimbs and cleft palate. The dose of 100 mcg/kg/day corresponds to a systemic exposure (AUC) of approximately 50-90 times the exposures observed in patients treated with the clinical tbo-filgrastim dose of 5 mcg/kg/day.

8.3 Nursing Mothers It is not known whether tbo-filgrastim is secreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when GRANIX is administered to a nursing woman. Other recombinant G-CSF products are poorly secreted in breast milk and G-CSF is not orally absorbed by neonates.

8.4 Pediatric Use The safety and effectiveness of GRANIX in pediatric patients have not been established.

8.5 Geriatric Use Among 677 cancer patients enrolled in clinical trials of GRANIX, a total of 111 patients were 65 years of age and older. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients.

8.6 Renal Impairment The safety and efficacy of GRANIX have not been studied in patients with moderate or severe renal impairment. No dose adjustment is recommended for patients with mild renal impairment.

8.7 Hepatic Impairment The safety and efficacy of GRANIX have not been studied in patients with hepatic impairment.

10 OVERDOSAGE No case of overdose has been reported. ©2014 Cephalon, Inc., a wholly-owned subsidiary of Teva Pharmaceutical Industries Ltd. All rights reserved.

GRANIX is a registered trademark of Teva Pharmaceutical Industries Ltd. Manufactured by: Distributed by: Sicor Biotech UAB Teva Pharmaceuticals USA, Inc. Vilnius, Lithuania North Wales, PA 19454 U.S. License No. 1803 Product of Israel GRX-40581 January 2015 This brief summary is based on TBO-004 GRANIX full Prescribing Information.

urinary or sexual dysfunction following radiotherapy, and patients with smaller prostate volumes had significantly better voiding and irritative outcomes when compared to larger volumes.”

As Rana explained, urinary symptoms and sexual dysfunction are the 2 most common complaints from patients following prostate radiotherapy, yet there are limited clinical data evaluating the effect of baseline patient characteristics on response to hypo­ fractionated treatment.

“While higher doses result in a lower risk of biochemical failure, they also increase the risk of bladder, rectal, and small bowel toxicity,” said Rana. “This study sought to evaluate how patient age and prostate size affects voiding symptoms, irritative symptoms, and sexual function, following SBRT.”

Urinary symptoms and sexual dysfunction are the 2 most common complaints from patients following prostate radiotherapy.

The retrospective analysis included 102 nonmetastatic patients treated with SBRT between May 2008 and September 2014. All patients received treatment at a single institution. The course of radiotherapy consisted of 36.25 Gy (range 35-40) over 5 daily fractions. IPSS and SHIM were recorded at baseline and 1, 3, 6, 9, 12, 18, 24, and 36 months after treatment.

Median patient age was 72 years (range 47-88). Median prostate volume was 43 cc (range 18.7-170.7).

Baseline IPSS irritative score, IPSS voiding score, and SHIM score were 5.21, 5.31, and 10.48, respectively.

“An increase in voiding (6.45), as well as a statistically significant increase in irritative symptoms (6.97), and significant decrease in SHIM score (11.95) were observed after 1 month (P<.05),” said Rana.

However, these changes proved to be transient.

“The IPSS irritative score and IPSS voiding scores returned to baseline in >75% of patients by 9 months and SHIM scores returned to baseline in >90% of patients by 2 years,” he reported.

Notably, prostate size ≤50 cc showed higher baseline IPSS voiding and Continued on page 6

www.TheOncologyNurse.com

MAY 2015 I VOL 8, NO 3

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EDITORIAL BOARD EDITOR-IN-CHIEF

Beth Faiman,

PhD, APRN-BC, AOCN

Cleveland Clinic Taussig Cancer Institute Cleveland, OH

Cassandra J. Hammond, RN, MSN, CRNP

Avid Education Partners, LLC Sharpsburg, MD

Catherine Bishop,

Shannon Hazen,

Johns Hopkins Kimmel Cancer Center/Sibley Infusion Washington, DC

BD Medical Surgical Systems Charlotte, NC

DNP, NP, AOCNP

Deena Damsky Dell, RN-BC, MSN, AOCN, LNC

Fox Chase Cancer Center Philadelphia, PA

Wendye DiSalvo,

DNP, APRN, AOCN Genentech New London, NH

Denice Economou,

RN, MN, CNS, AOCN City of Hope National Medical Center Duarte, CA

Somerset Medical Center Somerville, NJ

Taline Khoukaz,

Gary Shelton,

Keck Hospital of University of Southern California Norris Cancer Center Los Angeles, CA

Patient Advocacy Peg Ford

NYU Clinical Cancer Center New York, NY

Sandra E. Kurtin,

Lori Stover, RN,

Arizona Cancer Center Tucson, AZ

Western Pennsylvania Cancer Institute Pittsburgh, PA

Ann McNeill,

Joseph D. Tariman,

MSN, ACNP-C

RN, MS, AOCN, ANP-C

RN, MSN, APN

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

Millennium Pharmaceuticals, Inc Boston, MA

Dallas, TX

RJ Health Systems International, LLC Wethersfield, CT

BSc Pharm, RPh, FASCP

John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ

The CHE Consulting Group, Inc. Mt. Kisco, NY

Amy Ford, RN,

College of Nursing and Allied Health Professions University of Louisiana Lafayette, LA

RN, DNS

Nutrition Karen Connelly,

Kena C. Miller,

BSN, OCN

Pharmacy John F. Aforismo,

Jayshree Shah, RN, APN-C, AOCNP, MSN

RN, BSN, OCN

Constance Engelking, RN,

MS, CNS, OCN

Melinda G. Oberleitner,

RN, MSN, ARNP-BC

DNP(c), MSN, NP, ANP-BC, AOCNP

BSN

PhD, ANP-BC DePaul University Chicago, IL

Jacqueline Marie Toia, RN, MS, DNP Northwestern University Myeloma Program Chicago, IL

Ovarian Cancer Alliance of San Diego San Diego, CA

Social Work Carolyn Messner, DSW, LCSW-R, BCD, OSW-C CancerCare New York, NY

Genetic Counseling Cristi Radford, MS, CGC

Invitae Atlanta, GA

Managed Care and Pharmaceutical Management Burt Zweigenhaft, BS

Onco360/OncoMed New York, NY

Patricia Molinelli,

Connie Visovsky,

Somerset Medical Center Somerville, NJ

University of South Florida College of Nursing Tampa, FL

MS, RN, APN-C, AOCNS

RD, CSO

PhD, RN, ACNP-BC

Isabell Castellano, RN

Bristol-Myers Squibb Childrenâ&#x20AC;&#x2122;s Hospital Robert Wood Johnson University Hospital New Brunswick, NJ

Jeanne Westphal, RN Sharon S. Gentry,

Ellen A. Neylon,

Novant Health: Derrick L. Davis Cancer Center Winston-Salem, NC

Columbia University Medical Center Center for Lymphoid Malignancies New York, NY

RN, MSN, AOCN, CBCN

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MAY 2015 I VOL 8, NO 3

MSN, FNP-BC, CCRP, OCN

Rita Wickham,

Meeker Memorial Hospital Litchfield, MN

PhD, RN, AOCN

Northern Michigan University Independent Oncology & Palliative Care Consultant Marquette, MI

www.TheOncologyNurse.com

FROM THE EDITOR Welcome to this issue of The Oncology Nurse-APN/PA (TON). It’s gearing up to be a busy time of year for TON as we offer coverage of the recent Genitourinary Cancers Symposium and the National Comprehensive Cancer Network (NCCN) 20th Annual Conference. The next issue will have a focus on coverage of the Oncology Nursing Society 40th Annual Beth Faiman, PhD, APRN-BC, AOCN Congress. Needless to say, Editor-in-Chief we’re all taking deep breaths here at TON. The coverage from NCCN includes an article about how to best manage dermatologic toxicities that patients with cancer may develop as a result of their treatment.

Mario E. Lacouture, MD, presents some management strategies for skin rashes and related symptoms, nail changes, and alopecia and facial hirsutism—all possible adverse events that patients may experience. As Lacouture notes, improvements in survival “have given patients more opportunity to worry about their appearance and

quality of life.” That is the silver lining.

Another topic addresses the new NCCN clinical practice guideline for smoking cessation in oncology patients—it encourages the use of evidence-based pharmacotherapy, behavioral therapy, and close follow-up of any necessary re-treatment. The not-so-good news is that “virtually no institutions reported systemic and consistent mechanisms for fostering cessation.”

We address this issue in our new reader poll (see below). Visit www.TheOncologyNurse.com to let us know if you talk to your patients who smoke about how to best quit. Tell us if your institution has policies in place to help these patients.

In her Genetic Counseling column, Cristi Radford, MS, CGC, gives us an update about the latest research in inherited ovarian cancer—a very hot topic in the news.

Even though ovarian cancer accounts for 1.3% of all new cancers in the United States, it has a very high death rate as only about 1 in 7 women with the disease are diagnosed at the local stage.

As always, we at TON want to hear about your ideas and opinions. Please be sure to visit our website, www.

TheOncologyNurse.com, and tell us what topics you want to see covered in TON. We love to hear from you and we appreciate your feedback. n

PUBLISHING STAFF Vice President/Group Publisher Russell Hennessy rhennessy@the-lynx-group.com Vice President/Director of Sales & Marketing Joe Chanley jchanley@the-lynx-group.com Director, Client Services Dave Dempsey ddempsey@the-lynx-group.com Editorial Director Kristin Siyahian ksiyahian@the-lynx-group.com Managing Editor Kristen Olafson kolafson@the-lynx-group.com Copyeditors Mollie Friedman Peggy Roeske Production Manager Melissa Lawlor

THE LYNX GROUP President/CEO Brian Tyburski Chief Operating Officer Pam Rattananont Ferris

READER POLL Do you talk to your patients who smoke about how to quit? o Yes The NCCN has issued a new clinical practice guideline for smoking cessation in oncology patients. The guideline encourages the use of evidence-based pharmacotherapy, behavioral therapy, and close follow-up with re-treatment, if

o No

necessary. Many patients with cancer still smoke, which leads to worse outcomes when treated for their cancer. Do you talk to your patients about smoking cessation? Does your institution offer a program to help these patients?

Go to www.TheOncologyNurse.com to answer the question and add your comments.

Vice President of Finance Andrea Kelly Human Resources Jennine Leale Director, Strategy & Program Development John Welz Director, Quality Control Barbara Marino Quality Control Assistant Theresa Salerno Director, Production & Manufacturing Alaina Pede Director, Creative & Design Robyn Jacobs Creative & Design Assistants Lora LaRocca Wayne Williams Jr Digital Media Specialist Charles Easton IV Web Content Manager Anthony Trevean Digital Programmer Michael Amundsen Meeting & Events Planner Linda Mezzacappa Project Managers Deanna Martinez Jeremy Shannon Project Coordinator Rachael Baranoski

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It is the responsibility of the treating physician or other healthcare professional, relying on independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Every effort has been made to check generic and trade names, and to verify dosages. The ultimate responsibility, however, lies with the prescribing physician. Please convey any errors to the Editorial Director.

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MAY 2015 I VOL 8, NO 3

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CANCER CENTER PROFILE

Taussig Cancer Institute

Continued from the cover

What advice would you give to someone entering the field of oncology nursing?

At the Taussig Cancer Institute, clinical trials and research efforts ensure that patients have access to the latest advances in cancer treatment. Many support programs are available to help patients navigate the changes and challenges associated with cancer. Special services include patient education and support and wellness and prevention.

The Oncology Nurse-APN/PA interviewed Kimberly Hamilton, MSN, CNP, about her role as a nurse practitioner at Taussig Cancer Institute.

What is your role at the Taussig Cancer Institute?

Kimberly Hamilton (KH): I am a nurse practitioner [NP] working in an independent practice that follows patients with multiple myeloma and chronic leukemias. Patients are first seen by a hematologist/oncologist, diagnosed, and treatment initiated, and then we become part of their team. Patients are often seen monthly—one month by NPs and the next by the hematologist/oncologist. We also see patients for symptom management while they are here for treatment.

Patients with monoclonal gammop­ athy of undetermined significance (MGUS) are the exception. We see them independently and provide monitoring. We have created an algorithm of when to refer them to an oncologist that includes when they meet criteria for multiple myeloma or other disorders related to MGUS. I see about 8 to 12 patients per day, and this includes bone marrow biopsies.

Part of the role of NPs at Taussig is to staff the Cancer Associated Thrombosis (CAT) clinic. This is a separate clinic where patients can be evaluated if they are suspected of having a deep vein thrombosis or venous thromboembolism—they are treated the same day if necessary. These patients were previously sent to the emergency depart-

KH: Oncology is a specialty that encompasses all of the body’s systems and there are diverse types of cancer. I think that is part of what attracted me to the field—the diversity and the chance to learn about it. Diversity keeps things exciting and new. Oncology is a rapidly evolving field and there is a lot to keep up with. I think it is important to join professional organizations and to further one’s education.

Kimberly with her family. The twins are the reason why she would like a full-time maid and lawn care personnel!

ment. The CAT clinic is a new and unique aspect of our cancer institute that was started about a year ago.

What are the challenges of your job?

KH: In general, our main challenge is to make sure that patients who are living with a chronic cancer take care of their general health. That includes visits to the primary care physician, screening for second cancers, immunizations, and treatment for high cholesterol, hypertension, and diabetes. Cancer patients already have to have medical appointments and treatments and may feel that seeing a primary care doctor is one more doctor appointment that is burdensome, or they may assume that because they see us once a month that we are taking care of their general health, which is not the case. We encourage our patients to maintain a good relationship with their primary care provider.

What are the rewards of your job?

KH: It is gratifying to treat cancer patients and see that their overall function and symptoms are improved by our rec-

ommendations and that they can resume activities of daily life. We help them with their side effects from treatments, and other cancer-related symptoms that can include fatigue and bone pain.

What are you excited about in the field of oncology right now?

KH: I find cancer research exciting because it is a rapidly evolving field.

Here at Taussig we are involved in clinical trials of newer targeted therapies and other therapies. Recently panobinostat—a drug with a unique mechanism of action—was approved for the treatment of relapsed/refractory multiple myeloma in combination with Velcade [bortezomib]. We are now involved in clinical trials of panobino­ stat, as well as elotuzumab and newer compounds in multiple myeloma.

How has the role of the oncology nurse/NP changed in the past 5 years?

KH: The roles of the oncology nurse/ NP and physician assistant [PA] have evolved, and we are now recognized and appreciated as independent practitioners who provide care for cancer patients. NPs and PAs are in the frontline of care. We are the eyes and ears and we identify important issues that need to be addressed.

What would you do if you won the lottery? Would you still be an oncology NP?

KH: Yes, I would continue my work.

But I have 1-year-old twins, so I would hire a full-time maid and lawn care personnel. n

www.my.clevelandclinic.org/ services/cancer

What inspired you to become an oncology nurse?

KH: In college I decided that I wanted to be a nurse, and I worked as a nursing assistant in the hospice wing of a hospital, where I assisted with hospice and rehabilitation. These patients touched my heart, and I was encouraged by seeing that I could help meet their needs.

PROSTATE CANCER

Stereotactic Body Radiation Therapy... irritative resolution rates after 3 months (P<.05).

“With smaller prostate volumes, you are hitting less surrounding structures, which may be leading to a reduction in toxicity,” hypothesized Rana. “Patients with larger prostates tend to have higher doses hitting their bladder, urethra, etc. We have no histological proof of this, but in theory it’s feasible.”

Rana also noted several limitations

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to this study.

“The use of androgen-deprivation therapy [ADT] results in reduction of prostate size and could explain improvement in urinary symptoms following SBRT,” he said, “but this effect should be minimal as only 8.9% of the patient population studied used ADT.… Carefully controlled prospective trials should be conducted to confirm the effectiveness of SBRT in the

Continued from page 3

treatment of prostate cancer.”

Although Rana acknowledged the imprecision in comparing therapeutic strategies, he could not deny this study’s favorable results.

“Prostate cancer patients treated with SBRT exhibited minimal acute toxicity,” he concluded. “Three-year PSA response, reported toxicity, erectile function preservation, and urinary function improvement compare favor-

ably to data presented following radical prostatectomy, brachytherapy, or conventional external beam radiation therapy.” n

Reference

Rana ZH, Hong R, McRae D, et al. The impact of patient characteristics on voiding symptoms, irritative symptoms, and sexual function, following stereotactic body radiotherapy for prostate cancer. J Clin Oncol. 2015;33(suppl 7):abstract 245. Poster presented at: Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL.

www.TheOncologyNurse.com

BEST PRACTICES

Managing Dermatologic Toxicities • For ease of prescribing, become familiar with the brand name of one low-potency corticosteroid (to be used on the face and intertriginous areas) and one high-potency corticosteroid (to be used safely on other parts) and use those routinely; the pharmacist can substitute the generic.

• Prescribe topical corticosteroids in the form of creams, and in large tubes, since the involved area is often substantial.

• Treat rash associated with EGFR inhibitors prophylactically; do not wait for symptoms to appear.

• Evidence supports the prophylactic use of oral minocycline and doxycycline, which have been shown to reduce rash severity by about 50% or more, compared to “reactive” treatment. These agents may also reduce pruritus, secondary infections, and paronychia as well as nondermatologic toxicities grade 3 or higher (diarrhea, neutropenia, etc).

• Maintain a low threshold for culturing any lesion with discharge; secondary infections with a variety of organisms are common.

Xerosis (dry skin) often occurs further along in the treatment course. Moisturizing is best accomplished with creams that contain ammonium lactate, salicylic acid, or urea.

Pruritus usually responds to oral antihistamines and topical corticosteroids, but when severe it can be treated with the NK1 receptor inhibitor aprepitant. In a small study of patients whose itching was refractory to standard pruritus treatments, aprepitant achieved relief in 91% and itching recurred in only 13%.2

Nail Changes

Approximately 15% to 25% of patients undergoing treatment with EGFR and mTOR inhibitors can develop paronychia, a soft-tissue infection around the nail, as a result of nail-plate thinning and ingrowth. (See Figure 2.) Local treatment depends on paronychia severity. Mild cases can be treated with topical therapies; if there is discharge and a documented infection, an oral antibiotic is warranted. Soaking nails in a vinegar/ water solution can also be helpful. Grade 2-3 paronychia can be treated via cauterization with silver nitrate.

When patients do not respond to these measures, partial or complete nail avulsion (removing the nail plate) may be warranted. “This is initially scary to

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Figure 1 Acneiform Rash: EGFR Inhibitors

Continued from the cover

EGFR inhibition, and they also may be seen in patients with breast cancer being treated with the mTOR inhibitor everolimus or the monoclonal antibodies trastuzumab/pertuzumab. Lacouture recommended painting the nails with a hydrosoluble nail lacquer or the prescription product poly(urea-urethane) 16%.

Alopecia and Facial Hirsutism

Photo courtesy Mario E. Lacouture, MD/Memorial Sloan Kettering Cancer Center.

Figure 2 Paronychia: EGFR Inhibitors

Alopecia is a well-established side effect of numerous cytotoxic agents, but hair thinning can also occur with BRAF, MEK, EGFR, and hedgehog inhibitors. Lacouture made the following recommendations to prevent or manage hair loss: • Use bimatoprost for eyelash alopecia, which has been shown to increase length and thickness of eyelashes in chemotherapy patients.3 • Use scalp cooling (ie, “cold cap”) during chemotherapy, which in the 1400-patient Dutch Scalp Cooling Registry study allowed 50% of patients to eliminate head covers,4 and in a smaller study (N=70) prevented severe hair loss in 36% to 92% of patients (depending on the type of regimen).5 • Apply topical minoxidil, which reduces the duration of complete hair loss in patients by approximately 2 months.6 Another side effect of treatment with EGFR inhibitors is hirsutism of the face.

Lacouture recommends removing unwanted facial hair by threading or plucking—not with waxing or depilatories.

Other Toxicities Photos courtesy Mario E. Lacouture, MD/Memorial Sloan Kettering Cancer Center.

patients, but they are often very relieved after we do this,” Lacouture noted. Avulsion, which is usually well tolerated, can provide relief until the nail grows back, he said.

The nail changes induced by treatment with taxanes (especially docetaxel) are different from those induced by EGFR and mTOR inhibitors; elevation of the nail plate, inflammation, and sometimes bleeding and infection are seen. Severe nail changes can often be prevented by having the patient grip ice bags for 15 minutes before infusion, during treatment, and 15 minutes post infusion.

Brittle nails are also a consequence of

Hand-foot syndrome (HFS) can be seen with a variety of drugs, and its manifestations can differ by drug class.

The only randomized study of HFS prevention, conducted in patients receiving capecitabine, showed that prophylactic celecoxib 200 mg/day reduced HFS of grade 2 or higher by more than 50% versus control.7 Oral corticosteroids can be beneficial when HFS is due to liposomal doxorubicin. Though less supported by research, approaches that may ameliorate HFS induced by multikinase inhibitors include clobetasol foam, salicylic acid 6% cream, and lidocaine creams and patches.

For radiation-induced dermatitis, Lacouture recommended washing with soap and water. The medium-strength topical corticosteroid mometasone was also shown, in a randomized placebo-

controlled trial, to significantly reduce discomfort, itching, and redness.8 Lacouture did not recommend using topical nonsteroidal agents (trolamine), petrolatum ointment, or topical moisturizers, which have not proven effective.

Approximately 15% to 25% of patients undergoing treatment with EGFR and mTOR inhibitors can develop paronychia, a softtissue infection around the nail, as a result of nail-plate thinning and ingrowth.

These management suggestions may ameliorate dermatologic toxicity, which matters to patients now more than ever, Lacouture emphasized. Improvements in survival, he noted, “have given patients more opportunity to worry about their appearance and quality of life.” n

References

1. Lacouture ME. Management of dermatologic toxicities associated with targeted therapies. Presented at: National Comprehensive Cancer Network 20th Annual Conference; March 12-14, 2015; Hollywood, FL. http://nccnac2015.conferencespot.org/59242-nccn-1.

1948867/t-001-1.1948953/f-001-1.1948954/a-013-1.

1948958. Accessed April 5, 2015.

2. Santini D, Vincenzi B, Guida FM, et al. Aprepitant for management of severe pruritus related to biological cancer treatments: a pilot study. Lancet Oncol. 2012;13 (10):1020-1024.

3. Morris CL, Stinnett S, Woodward J. The role of bimatoprost eyelash gel in chemotherapy-induced madarosis: an analysis of efficacy and safety. Int J Trichology. 2011;3(2):84-91.

4. van den Hurk CJ, Peerbooms M, van de Poll-Franse LV, et al. Scalp cooling for hair preservation and associated characteristics in 1411 chemotherapy patients—results of the Dutch Scalp Cooling Registry.

Acta Oncol. 2012;51(4):497-504.

5. Katsimbri P, Bamias A, Pavlidis N. Prevention of chemotherapy-induced alopecia using an effective scalp cooling system. Eur J Cancer. 2000;36(6):766-771.

6. Duvic M, Lemak NA, Valero V, et al. A randomized trial of minoxidil in chemotherapy-induced alopecia.

J Am Acad Dermatol. 1996;35(1):74-78.

7. Zhang RX, Wu XJ, Lu SX, et al. The effect of COX-2 inhibitor on capecitabine-induced hand-foot syndrome in patients with stage II/III colorectal cancer: a phase II randomized prospective study. J Cancer Res Clin Oncol. 2011;137(6):953-957.

8. Miller RC, Schwartz DJ, Sloan JA, et al. Mometasone furoate effect on acute skin toxicity in breast cancer patients receiving radiotherapy: a phase III double-blind, randomized trial from the North Central Cancer Treatment Group N06C4. Int J Radiat Oncol Biol Phys. 2011;79(5):1460-1466.

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BEST PRACTICES

Maximizing Efficacy in the Infusion Unit: Making Patients and Nurses Happy Audrey Andrews

O

ncology nurses in the University of Miami Health System were able to significantly increase efficiency, reduce waiting time, and treat more patients each day in their outpatient oncology infusion suite by revamping scheduling and using a master template. They described their success at the National Comprehensive Cancer Network 20th Annual Conference, held recently in Hollywood, Florida.

“We were in a state of chaos. We looked at the needs of our nurses, and what our patients were saying, and, while there are always constraints in the system, we knew we had to make things better,” said Angela Olier-Pino, DNP, MBA, RN. First author Gloria G. Campos, MSIE, an industrial engineer, explained, “We were trying to make sure we aligned treatment durations to how they were reflected on the schedule.

We investigated patient waiting times and learned that their appointment times were not aligning with the times that patients were arriving. We put together a multidisciplinary team to review these time blocks, to determine what each treatment looked like.”

The group’s goal was to ensure that capacity matched scheduled treatment times. They wanted to reduce patient wait time (from arrival to treatment chair) and diminish the variance between the actual and scheduled chair times. By improving the scheduling of patient chair time, the nurses could better manage their resources and nursing capacity, and this would consequently reduce patient wait times.

A multidisciplinary team of nurses and pharmacists standardized the

scheduling guidelines to approximate treatment chair time for patients and nursing acuity (ie, difficulty). They did this by examining nursing documentation and the time required for infusion, postinfusion monitoring, patient education, pharmacy and laboratory turnaround, medication and its reconstitution, and preinfusion examinations (such as echocardiograms).

They developed master templates to operationalize the scheduling guidelines, which ensured that capacity was maximized; four templates hosted 30-minute slots, with staggered start and end times. Nursing schedules were aligned to match the maximum capacity in the templates.

Improvements on Multiple Measures

Success was evaluated based on the impact on 3 key measures, comparing outcomes at baseline and after implementation. The first was scheduled versus actual treatment duration, for which the mean and the variance decreased significantly. This indicated less tendency to overestimate the duration of treatment and improved predictability, which optimized the use of resources.

“We were overestimating treatment durations by 20 minutes,” Campos noted. At baseline, the difference between scheduled versus actual treatment time was 21 minutes, which dropped to less than 10 minutes after implementation of the program, a 53% difference.

The second measure was the percentage of patients whose actual treatment duration was within 30 minutes

of the scheduled treatment duration.

Patients whose treatment length (total time in the chair) was predicted within a 30-minute margin of error increased significantly, allowing nurses to utilize chair time more accurately.

At baseline, 31% of patients had a treatment time that varied by 30 minutes or so from the predicted treatment duration. This dropped to 16% after implementation, a 50% difference.

Better scheduling and efficiency allowed the nurses to treat 40 additional patients per day.

The third measure was patient wait times (arrival time to the chair), which was reduced by more than 15 minutes.

This increased the predictability of the total treatment duration, which allowed for timely use of resources.

The mean wait time was 45 minutes at baseline, dropping to 30 minutes under the new program, a 33% improvement per day per patient.

Better scheduling and efficiency allowed the nurses to treat 40 additional patients per day. The unit averaged 60 patients at baseline, but it now averages 100 within the same number of hours, with the same number of chairs, and with the same average of 17 nurses per day.

More Predictability Means Nurses Are Happier

Lauren Gjolaj, MBA, BSN, RN,

added that the new structure makes the nurses’ workday more predictable, and while more patients are being treated the workload does not seem greater.

“The chaos has been reduced,” she said. “Before, patients were scheduled incorrectly, creating hours of crunch time and hours of downtime. The manner in which we see patients is more stable.”

The nurses staggered the infusion start and end times to ensure that chairs remained filled, and they matched nurses’ schedules to the start and end times to ensure the optimal number of staff for patients. They also figured nursing acuity into the scheduling. “The staff doing the scheduling were not all clinical, and we were not all speaking the same language, so we talked to the schedulers about how to best handle the different situations,” Gjolaj said.

“This helped them make better decisions when filling in the [scheduling] template.”

Under the new system, the schedule was based not only on the number of patients per day per nurse, but on the acuity of the individual patient and regimen. This assured equal distribution of work among the nurses.

Olier-Pino added that the number of patients and nurses is now more appropriate, and nurses are rarely being asked to extend their shifts. “We were having to beg nurses to stay and to pay overtime,” she said. “Morale is much better now.” n

Reference

Campos GG, et al. Improving efficiency and capacity via cancer treatment scheduling standardization. Presented at: National Comprehensive Cancer Network 20th Annual Conference; March 12-14, 2015; Hollywood, FL.

New NCCN Guideline Addresses Smoking Cessation in Patients With Cancer Wayne Kuznar

A

new clinical practice guideline for smoking cessation in oncology patients encourages use of evidence-based pharmacotherapy, behavioral therapy, and close follow-up with re-treatment, if needed, said Peter Shields, MD, Deputy Director, the Ohio State University Comprehensive Cancer Center, Columbus, at the National Comprehensive Cancer Network (NCCN) 20th Annual Conference,

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held in March in Hollywood, Florida.

According to the American Association for Cancer Research Task Force on Tobacco, “virtually no institutions reported systematic and consistent mechanisms for fostering cessation,” said Shields.

Many cancer patients still smoke, and those who do have worse outcomes when treated for their cancer, he said, citing at least 1 study on the

negative influence of smoking on the efficacy of radiation therapy in head and neck cancer.

Shields noted that cancer patients who smoke are typically more nicotine dependent and probably have a history of unsuccessful attempts to quit. The most effective treatment approach at any point in the NCCN guideline algorithm is a combination of pharmacologic therapy and coun-

seling. Nicotine replacement therapy (NRT) alone may be no better than unaided quitting, and a dose-response relationship exists between the amount of therapy and success. “Brief counseling, even as short as 3 minutes, is better than no counseling,” said Shields. Behavioral therapy can take the form of individual in-person counseling, phone counseling, or group counseling. www.TheOncologyNurse.com

BEST PRACTICES

New NCCN Guideline Addresses...

Smoking status should be documented in patient health records and updated at regular intervals. Healthcare providers should discuss relapse and provide guidance for patients.

Smoking relapse may or may not warrant a change in therapy. “Sometimes smokers require repeated quit attempts with the same therapies as smoking slips, and relapses are common,” he said.

In addition to NRT, varenicline is considered a first-line pharmacologic treatment. Second-line pharmacologic options are varenicline plus NRT and bupropion plus NRT. Third-line options are varenicline plus bupropion with or without NRT, the tricyclic antidepressant nortriptyline, and the alpha-2 adrenergic receptor agonist clonidine.

Bupropion is contraindicated for patients with seizure risk, and users of varenicline and bupropion should be

monitored for new or worsening neuropsychiatric issues. For NRT, there is no evidence that nicotine itself causes cancer or increases the risk of heart disease.

The guideline calls for an evaluation

Continued from page 8

A review of the risks of smoking and benefits of quitting should be performed in patients who are not ready to quit. Barriers to quitting should be addressed, and educational resources provided. Encouraging

Smoking status should be documented in patient health records and updated at regular intervals.

Healthcare providers should discuss relapse and provide guidance for patients. of the patient’s current smoking status, and “prioritizes those likely to relapse,” said Shields. “Current smokers and those smoking within 30 days are treated the same.” These patients should have their readiness to quit assessed.

Those ready to quit should be given a personalized plan that includes the smoking cessation therapies mentioned above.

these patients to reduce the number of cigarettes per day could pay dividends, said Shields, as they may be more apt to try to quit altogether if they find they can successfully reduce the number of cigarettes smoked each day.

Former smokers and those who quit recently (within 30 days) should be evaluated for their risk of relapse.

Those deemed at high risk for relapse should be considered for pharmacotherapy and behavioral therapy and offered support resources. In those deemed at low risk for relapse, the success and importance of remaining abstinent should be reinforced, and their risk of relapse should be assessed at every visit.

The guideline does not recommend electronic cigarettes as an aid for smoking cessation because of insufficient evidence to support their use. The same goes for acupuncture, hypnosis, and nutritional supplements. Further, how electronic cigarettes and alternate therapies might interfere with proven methods for quitting is unknown, said Shields. n

Reference

Shields PG. New NCCN guidelines: smoking cessation for patients with cancer. Presented at: 20th National Comprehensive Cancer Network Annual Conference; March 12-14, 2015; Hollywood, FL.

Noteworthy Numbers Colorectal Cancer

Among cancers that affect both men and women, colorectal cancer (CRC) is the second leading cause of death. The American Cancer Society estimates that in 2015 there will be 93,090 new cases of colon cancer; 39,610 new cases of rectal cancer; and 49,700 deaths from both.1 As part of the effort to prevent colon cancer, the Centers for Disease Control and Prevention (CDC) maintains the Colorectal Cancer Control Program (CRCCP), which provides funding in 25 states, as well as to 4 Native American tribal organizations. The goal is to increase colorectal cancer screening among men and women aged 50 years and older from an estimated 64% to 80%.

Between 2009 and 2013, the CRCCP helped fund approximately 50,000 screenings, and 141 colorectal cancers and 6838 cases of precancerous adenomatous polyps were diagnosed.2,3 Using CRC data from the Surveillance, Epidemiology, and End Results (SEER) registry, researchers at the MD Anderson Cancer Center evaluated 64,157 patients diagnosed with stage IV colon or rectal cancer. From 1988 to 2010 inclusive, surgery rates decreased from 74.5% to 57.4%. The

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median survival rate improved from 8.6% in 1988 to 17.8% in 2009. The shift away from surgery began in 2001 as effective treatment options, including chemotherapy and biological therapy, became available.4 Researchers at the Dana-Farber Cancer Institute report that clinical trial patients with newly diagnosed advanced CRC who had high levels of vitamin D in their blood before chemotherapy and treatment with targeted drugs survived longer, on average, than patients with lower levels. Vitamin D levels were measured in 1043 patients when they enrolled in a phase 3 trial of 3 different drug combinations. The average level for all patients in the trial was 17.2 ng/mL (range: 8 ng/mL-27.5 ng/mL). Patients with the highest levels survived 33% longer than those with the lowest levels (32.6 months vs 24.5 months).5

In a study to assess the risk of CRC associated with type 2 diabetes, 300,039 patients with diabetes were compared with a matched number of people without diabetes.

After a median follow-up of 4.5 years, 2759 CRC cases were found among the patients with diabetes, representing a moderate 1.3-fold increased risk of CRC compared with nondiabetic subjects. Among diabetic patients, a trend of increased CRC risk was seen with duration of obesity ≥4 years.6

Sources

1. http://www.cancer.org/acs/groups/ content/@editorial/documents/ document/acspc-044514.pdf.

2. http://www.cdc.gov/cancer/crccp/.

3. http://m.cdc.gov/en/HealthSafetyTopics/Diseases Conditions/Cancer/Related/CRCCP. 4. http://www.ncbi.nlm.nih.gov/pubmed/25588105.

5. http://www.sciencedaily.com/ releases/2015/01/150113111119.htm.

6. http://care.diabetesjournals.org/content/ early/2014/12/18/dc14-1175.abstract.

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For patients with bone metastases from solid tumors

Prevent bone complications longer In a prespecified integrated analysis of 3 pivotal trials (N = 5,723),

8.2

XGEVA® was proven to delay the median time to first bone complication by

months longer vs zoledronic acid1

XGEVA® is a convenient 120 mg subcutaneous injection administered once every 4 weeks.2

Bone complications, or skeletal-related events (SREs), are defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression.2,3 Median Time to First Bone Complication1 27.7

months

Data from a prespecified integrated analysis of three international, phase 3, double-blind, double-dummy, active-controlled trials comparing XGEVA® with zoledronic acid for the prevention of bone complications in patients with bone metastases from solid tumors or multiple myeloma.1

XGEVA VA® 120 mg Q4W (n = 2,862) VA

19.5

months

zoledronic acid 4 mg Q4W (n = 2,861) 1 YEAR

HR* = 0.83 (95% CI: 0.76-0.90)

2 YEARS

P < 0.001

†

IMPORTANT SAFETY INFORMATION Hypocalcemia • Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA®. XGEVA® can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Monitor levels more frequently when XGEVA® is administered with other drugs that can also lower calcium levels. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.

• An increased risk of hypocalcemia has been observed in clinical trials of patients with increasing renal dysfunction, most commonly with severe dysfunction (creatinine clearance less than 30 mL/minute and/or on dialysis), and with inadequate/no calcium supplementation.

Monitor calcium levels and calcium and vitamin D intake.

Hypersensitivity • XGEVA® is contraindicated in patients with known clinically significant hypersensitivity to XGEVA®, including anaphylaxis that has been reported with use of XGEVA®.

Reactions may include hypotension, dyspnea, upper airway edema, lip swelling, rash, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue XGEVA® therapy permanently.

*Hazard ratio (HR) is defined as the increase or decrease in likelihood of an event of interest (in this case a bone complication) for one group relative to that in a comparator group.

P value for superiority.

†

Drug Products with Same Active Ingredient • Patients receiving XGEVA® should not take Prolia® (denosumab).

Osteonecrosis of the Jaw • Osteonecrosis of the jaw (ONJ) can occur in patients receiving XGEVA®, manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion. Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ. In clinical trials in patients with osseous metastasis, the incidence of ONJ was higher with longer duration of exposure.

• Perform an oral examination and appropriate preventive dentistry prior to the initiation of XGEVA® and periodically during XGEVA® therapy. Advise patients regarding oral hygiene practices. Avoid invasive dental procedures during treatment with XGEVA®.

• Patients who are suspected of having or who develop ONJ while on XGEVA® should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.

Atypical Subtrochanteric and Diaphyseal Femoral Fracture • Atypical femoral fracture has been reported with XGEVA®.

These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution.

XGEVA® is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

XGEVA® is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.

• RANK Ligand (RANKL) is produced by bone cells in the skeleton and is a key mediator of bone resorption4 • RANKL production is increased at sites of bone metastases, and stimulates osteoclasts to destroy bone4 • XGEVA® acts precisely to bind RANKL and inhibits osteoclast formation, function, and survival2 • Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA®2

Learn more at XGEVA.com

• Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture. During XGEVA® treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patient presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of XGEVA® therapy should be considered, pending a risk/benefit assessment, on an individual basis.

Embryo-Fetal Toxicity • XGEVA® can cause fetal harm when administered to a pregnant woman. Based on findings in animals, XGEVA® is expected to result in adverse reproductive effects.

©2014 Amgen Inc. All rights reserved. 04/14 80218-R1-V1

• Advise females of reproductive potential to use highly effective contraception during therapy, and for at least 5 months after the last dose of XGEVA®. Apprise the patient of the potential hazard to a fetus if XGEVA® is used during pregnancy or if the patient becomes pregnant while patients are exposed to XGEVA®.

Adverse Reactions • The most common adverse reactions in patients receiving XGEVA® with bone metastasis from solid tumors were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction was dyspnea. The most common adverse reactions resulting in discontinuation were osteonecrosis and hypocalcemia.

Please see brief summary of Prescribing Information on the following page.

REFERENCES: 1. Lipton A, Fizazi K, Stopeck AT, et al. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials.

Eur J Cancer. 2012;48:3082-3092. 2. XGEVA® (denosumab) prescribing information, Amgen. 3. Brodowicz T, O’Byrne K, Manegold C. Bone matters in lung cancer. Ann Oncol. 2012;23:2215-2222. 4. Roodman GD. Mechanisms of bone metastasis. N Engl J Med. 2004;350:1655-1664.

www.XGEVA.com

S:9.5”

Brief Summary: Consult package insert for complete Prescribing Information

Body System GASTROINTESTINAL Nausea Diarrhea GENERAL Fatigue/ Asthenia IN VESTIGATIONS Hypocalcemiab Hypophosphatemiab NEUROLOGICAL Headache RESPIRATORY Dyspnea Cough

Xgeva n = 2841 %

Zoledronic Acid n = 2836 %

31 20

32 19

45

46

18 32

9 20

13

14

21 15

18 15

Adverse reactions reported in at least 10% of patients receiving Xgeva in Trials 1, 2, and 3, and meeting one of the following criteria: • At least 1% greater incidence in Xgeva-treated patients, or • Between-group difference (either direction) of less than 1% and more than 5% greater incidence in patients treated with zoledronic acid compared to placebo (US Prescribing Information for zoledronic acid) b Laboratory-derived and below the central laboratory lower limit of normal [8.3 – 8.5 mg/dL (2.075 – 2.125 mmol/L) for calcium and 2.2 – 2.8 mg/dL (0.71 – 0.9 mmol/L) for phosphorus] Severe Mineral/Electrolyte Abnormalities • Severe hypocalcemia (corrected serum calcium less than 7 mg/dL or less than 1.75 mmol/L) occurred in 3.1% of patients treated with Xgeva and 1.3% of patients treated with zoledronic acid. Of patients who experienced severe hypocalcemia, 33% experienced 2 or more episodes of severe hypocalcemia and 16% experienced 3 or more episodes.

• Severe hypophosphatemia (serum phosphorus less than 2 mg/dL or less than 0.6 mmol/L) occurred in 15.4% of patients treated with Xgeva and 7.4% of patients treated with zoledronic acid.

Osteonecrosis of the Jaw In the primary treatment phases of Trials 1, 2, and 3, ONJ was confirmed in 1.8% of patients in the Xgeva group (median exposure of 12.0 months; range 0.1 – 40.5) and 1.3% of patients in the zoledronic acid group. The trials in patients with breast (Trial 1) or prostate (Trial 3) cancer included an Xgeva open label extension treatment phase where patients were offered Xgeva 120 mg once every 4 weeks (median overall exposure of 14.9 months; range 0.1 – 67.2). The patient-year adjusted incidence of confirmed ONJ was 1.1% during the first year of treatment and 4.1% thereafter. The median time to ONJ was 20.6 months (range: 4 – 53).

Atypical Subtrochanteric and Diaphyseal Fracture Atypical femoral fracture has been reported with Xgeva.

Postmarketing Experience. Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions have been identified during post approval use of Xgeva: • Hypocalcemia: Severe symptomatic hypocalcemia, including fatal cases.

• Hypersensitivity, including anaphylactic reactions.

• Musculoskeletal pain, including severe musculoskeletal pain. Positive rechallenge has been reported.

Immunogenicity. As with all therapeutic proteins, there is potential for immunogenicity. Using an electrochemiluminescent bridging immunoassay, less than 1% (7/2758) of patients with osseous metastases treated with denosumab doses ranging from 30 – 180 mg every 4 weeks or every 12 weeks for up to 3 years tested positive for binding antibodies. No patient with positive binding antibodies tested positive for neutralizing antibodies as assessed using a chemiluminescent cell-based in vitro biological assay. There was no evidence of altered pharmacokinetic profile, toxicity profile, or clinical response associated with binding antibody development. The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of a positive antibody (including neutralizing antibody) test result may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of antibodies to denosumab with the incidence of antibodies to other products may be misleading.

DRUG INTERACTIONS: No formal drug-drug interaction trials have been conducted with Xgeva. In clinical trials in patients with breast cancer metastatic to bone, Xgeva was administered in combination with standard anticancer treatment. Serum denosumab concentrations at 1 and 3 months and reductions in the bone turnover marker uNTx/Cr (urinary N-terminal telopeptide corrected for creatinine) at 3 months were similar in patients with and without prior intravenous bisphosphonate therapy.

There was no evidence that various anticancer treatments affected denosumab systemic exposure and pharmacodynamic effect. Serum denosumab concentrations at 1 and 3 months were not altered by concomitant chemotherapy and/or hormone therapy. The median reduction in uNTx/Cr from baseline to month 3 was similar between patients receiving concomitant chemotherapy and/or hormone therapy.

USE IN SPECIFIC POPULATIONS: Pregnancy: Category D. Risk Summary: Xgeva can cause fetal harm when administered to a pregnant woman based on findings in animals. In utero denosumab exposure in cynomolgus monkeys resulted in increased fetal loss, stillbirths, and postnatal mortality, along with evidence of absent lymph nodes, abnormal bone growth and decreased neonatal growth. There are no adequate and well-controlled studies with Xgeva in pregnant women. Women should be advised not to become pregnant when taking Xgeva. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women who become pregnant during Xgeva treatment are encouraged to enroll in Amgen’s Pregnancy Surveillance Program. Patients or their physicians should call 1-800-77-AMGEN (1-800-772-6436) to enroll.

Clinical Considerations: The effects of Xgeva are likely to be greater during the second and third trimesters of pregnancy. Monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the third trimester. If the patient becomes pregnant during Xgeva therapy, consider the risks and benefits in continuing or discontinuing treatment with Xgeva. a

Animal Data: The effects of denosumab on prenatal development have been studied in both cynomolgus monkeys and genetically engineered mice in which RANK ligand (RANKL) expression was turned off by gene removal (a “knockout mouse”).

In cynomolgus monkeys dosed subcutaneously with denosumab throughout pregnancy at a pharmacologically active dose, there was increased fetal loss during gestation, stillbirths, and postnatal mortality. Other findings in offspring included absence of axillary, inguinal, mandibular, and mesenteric lymph nodes; abnormal bone growth, reduced bone strength, reduced hematopoiesis, dental dysplasia and tooth malalignment; and decreased neonatal growth. At birth out to one month of age, infants had measurable blood levels of denosumab (22-621% of maternal levels). Following a recovery period from birth out to 6 months of age, the effects on bone quality and strength returned to normal; there were no adverse effects on tooth eruption, though dental dysplasia was still apparent; axillary and inguinal lymph nodes remained absent, while mandibular and mesenteric lymph nodes were present, though small; and minimal to moderate mineralization in multiple tissues was seen in one recovery animal. There was no evidence of maternal harm prior to labor; adverse maternal effects occurred infrequently during labor.

Maternal mammary gland development was normal. There was no fetal NOAEL (no observable adverse effect level) established for this study because only one dose of 50 mg/kg was evaluated. In RANKL knockout mice, absence of RANKL (the target of denosumab) also caused fetal lymph node agenesis and led to postnatal impairment of dentition and bone growth. Pregnant RANKL knockout mice showed altered maturation of the maternal mammary gland, leading to impaired lactation.

Nursing Mothers. It is not known whether Xgeva is excreted into human milk.

Measurable concentrations of denosumab were present in the maternal milk of cynomolgus monkeys up to 1 month after the last dose of denosumab (≤ 0.5% milk:serum ratio). Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Xgeva, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Maternal exposure to Xgeva during pregnancy may impair mammary gland development and lactation based on animal studies in pregnant mice lacking the RANK/RANKL signaling pathway that have shown altered maturation of the maternal mammary gland, leading to impaired lactation postpartum. However, in cynomolgus monkeys treated with denosumab throughout pregnancy, maternal mammary gland development was normal, with no impaired lactation. Mammary gland histopathology at 6 months of age was normal in female offspring exposed to denosumab in utero; however, development and lactation have not been fully evaluated.

Pediatric Use. Xgeva is not recommended in pediatric patients. The safety and effectiveness of Xgeva in pediatric patients have not been established. Treatment with Xgeva may impair bone growth in children with open growth plates and may inhibit eruption of dentition. In neonatal rats, inhibition of RANKL (the target of Xgeva therapy) with a construct of osteoprotegerin bound to Fc (OPG-Fc) at doses ≤ 10 mg/kg was associated with inhibition of bone growth and tooth eruption.

Adolescent primates treated with denosumab at doses 5 and 25 times (10 and 50 mg/kg dose) higher than the recommended human dose of 120 mg administered once every 4 weeks, based on body weight (mg/kg), had abnormal growth plates, considered to be consistent with the pharmacological activity of denosumab.

Cynomolgus monkeys exposed in utero to denosumab exhibited bone abnormalities, reduced hematopoiesis, tooth malalignment, decreased neonatal growth, and an absence of axillary, inguinal, mandibular, and mesenteric lymph nodes. Some bone abnormalities recovered once exposure was ceased following birth; however, axillary and inguinal lymph nodes remained absent 6 months post-birth.

Geriatric Use. Of patients who received Xgeva in Trials 1, 2, and 3, 1260 (44%) were 65 years of age or older. No overall differences in safety or efficacy were observed between these patients and younger patients.

Renal Impairment. Two clinical trials were conducted in patients without cancer and with varying degrees of renal function. In one study, patients (N=55) with varying degrees of renal function (ranging from normal through end-stage renal disease requiring dialysis) received a single 60 mg subcutaneous dose of denosumab. In a second study, patients (N=32) with severe renal dysfunction (creatinine clearance less than 30 mL/minute and/or on dialysis) were given two 120 mg subcutaneous doses of denosumab. In both studies, greater risk of developing hypocalcemia was observed with increasing renal impairment, and with inadequate/no calcium supplementation. Hypocalcemia was mild to moderate in severity in 96% of patients.

Monitor calcium levels and, calcium and vitamin D intake.

Females and Males of Reproductive Potential. Contraception Females: Counsel patients on pregnancy planning and prevention. Advise females of reproductive potential to use highly effective contraception during therapy, and for at least 5 months after the last dose of Xgeva. Advise patients to contact their healthcare provider if they become pregnant, or a pregnancy is suspected, during treatment or within 5 months after the last dose of Xgeva. Males: The extent to which denosumab is present in seminal fluid is unknown. There is potential for fetal exposure to denosumab when a male treated with Xgeva has unprotected sexual intercourse with a pregnant partner. Advise males of this potential risk.

OVERDOSAGE: There is no experience with overdosage of Xgeva.

HOW SUPPLIED/STORAGE AND HANDLING: Xgeva is supplied in a singleuse vial. Store Xgeva in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton. Do not freeze. Once removed from the refrigerator, Xgeva must not be exposed to temperatures above 25°C/77°F or direct light and must be used within 14 days. Discard Xgeva if not used within the 14 days. Do not use Xgeva after the expiry date printed on the label. Protect Xgeva from direct light and heat. Avoid vigorous shaking of Xgeva.

PATIENT COUNSELING INFORMATION: Advise patients to contact a healthcare professional for any of the following: • Symptoms of a hypersensitivity reaction, including rash, urticaria, pruritus, lip swelling, shortness of breath, hypotension and respiratory tract edema • Symptoms of hypocalcemia, including paresthesias or muscle stiffness, twitching, spasms, or cramps • Symptoms of ONJ, including pain, numbness, swelling of or drainage from the jaw, mouth, or teeth • Persistent pain or slow healing of the mouth or jaw after dental surgery • Symptoms of atypical femoral fracture, including new or unusual thigh, hip, or groin pain • Pregnancy or nursing Advise patients of the need for: • Avoiding therapy with Xgeva if a serious allergic reaction occurred with prior Xgeva or Prolia therapy • Proper oral hygiene and routine dental care • Informing their dentist that they are receiving Xgeva • Avoiding invasive dental procedures during treatment with Xgeva • The use of highly effective contraception during and for at least 5 months after treatment with Xgeva for females of reproductive potential Advise patients that denosumab is also marketed as Prolia®. Patients should inform their healthcare provider if they are taking Prolia.

Amgen Manufacturing Limited, a subsidiary of Amgen Inc. One Amgen Center Drive Thousand Oaks, California 91320-1799 ©2010-2014 Amgen Inc. All rights reserved.

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INDICATIONS AND USAGE: Bone Metastasis from Solid Tumors. Xgeva is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

Important Limitation of Use. Xgeva is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.

DOSAGE AND ADMINISTRATION: Recommended Dosage. The recommended dose of Xgeva is 120 mg administered as a subcutaneous injection every 4 weeks in the upper arm, upper thigh, or abdomen. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia.

Preparation and Administration. Visually inspect Xgeva for particulate matter and discoloration prior to administration. Xgeva is a clear, colorless to pale yellow solution that may contain trace amounts of translucent to white proteinaceous particles. Do not use if the solution is discolored or cloudy or if the solution contains many particles or foreign particulate matter. Prior to administration, Xgeva may be removed from the refrigerator and brought to room temperature (up to 25°C/77°F) by standing in the original container. This generally takes 15 to 30 minutes. Do not warm Xgeva in any other way. Use a 27-gauge needle to withdraw and inject the entire contents of the vial. Do not re-enter the vial. Discard vial after single-use or entry.

CONTRAINDICATIONS: Hypocalcemia. Pre-existing hypocalcemia must be corrected prior to initiating therapy with Xgeva.

Hypersensitivity. Xgeva is contraindicated in patients with known clinically significant hypersensitivity to Xgeva.

WARNINGS AND PRECAUTIONS: Drug Products with Same Active Ingredient. Xgeva includes the same active ingredient (denosumab) found in Prolia. Patients receiving Xgeva should not take Prolia.

Hypersensitivity. Clinically significant hypersensitivity including anaphylaxis has been reported with use of Xgeva. Reactions may include hypotension, dyspnea, upper airway edema, lip swelling, rash, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue Xgeva therapy permanently.

Hypocalcemia. Xgeva can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Correct pre-existing hypocalcemia prior to Xgeva treatment. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Monitor levels more frequently when Xgeva is administered with other drugs that can also lower calcium levels. In the postmarketing setting, severe symptomatic hypocalcemia has been reported. Advise patients to contact a healthcare professional for symptoms of hypocalcemia. An increased risk of hypocalcemia has been observed in clinical trials of patients with increasing renal dysfunction, most commonly with severe dysfunction (creatinine clearance less than 30 mL/minute and/or on dialysis), and with inadequate/no calcium supplementation. Monitor calcium levels and calcium and vitamin D intake.

Osteonecrosis of the Jaw. Osteonecrosis of the jaw (ONJ) can occur in patients receiving Xgeva, manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion.

Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ. In clinical trials, in patients with osseous metastasis, the incidence of ONJ was higher with longer duration of exposure (see Adverse Reactions). Seventy-nine percent of patients with ONJ had a history of tooth extraction, poor oral hygiene, or use of a dental appliance as a predisposing factor. Perform an oral examination and appropriate preventive dentistry prior to the initiation of Xgeva and periodically during Xgeva therapy. Advise patients regarding oral hygiene practices. Avoid invasive dental procedures during treatment with Xgeva. Patients who are suspected of having or who develop ONJ while on Xgeva should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.

Atypical Subtrochanteric and Diaphyseal Femoral Fracture. Atypical femoral fracture has been reported with Xgeva. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution. Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture. During Xgeva treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patient presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of Xgeva therapy should be considered, pending a risk/benefit assessment, on an individual basis.

EMBRYO-FETAL TOXICITY: Xgeva can cause fetal harm when administered to a pregnant woman. Based on findings in animals, Xgeva is expected to result in adverse reproductive effects. In utero denosumab exposure in cynomolgus monkeys resulted in increased fetal loss, stillbirths, and postnatal mortality, along with evidence of absent peripheral lymph nodes, abnormal bone growth, and decreased neonatal growth (see Use in Specific Populations). Advise females of reproductive potential to use highly effective contraception during therapy, and for at least 5 months after with the last dose of Xgeva. Apprise the patient of the potential hazard to a fetus if Xgeva is used during pregnancy or if the patient becomes pregnant while patients are exposed to Xgeva. Advise patients to contact their healthcare provider if they become pregnant or a pregnancy is suspected during this time.

ADVERSE REACTIONS: The following adverse reactions are discussed below and elsewhere in the labeling: • Hypocalcemia • Osteonecrosis of the Jaw The most common adverse reactions in patients receiving Xgeva (per-patient incidence greater than or equal to 25%) were fatigue/asthenia, hypophosphatemia, and nausea (see Table 1). The most common serious adverse reaction in patients receiving Xgeva was dyspnea. The most common adverse reactions resulting in discontinuation of Xgeva were osteonecrosis and hypocalcemia.

Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in practice. The safety of Xgeva was evaluated in three randomized, double-blind, double-dummy trials in which a total of 2841 patients with bone metastasis from prostate cancer, breast cancer, or other solid tumors, or lytic bony lesions from multiple myeloma received at least one dose of Xgeva. In Trials 1, 2, and 3, patients were randomized to receive either 120 mg of Xgeva every 4 weeks as a subcutaneous injection or 4 mg (dose adjusted for reduced renal function) of zoledronic acid every 4 weeks by intravenous (IV) infusion. Entry criteria included serum calcium (corrected) from 8 to 11.5 mg/dL (2 to 2.9 mmol/L) and creatinine clearance 30 mL/min or greater. Patients who had received IV bisphosphonates were excluded, as were patients with prior history of ONJ or osteomyelitis of the

jaw, an active dental or jaw condition requiring oral surgery, non-healed dental/ oral surgery, or any planned invasive dental procedure. During the study, serum chemistries including calcium and phosphorus were monitored every 4 weeks.

Calcium and vitamin D supplementation was recommended but not required. The median duration of exposure to Xgeva was 12 months (range: 0.1 – 41) and median duration on-study was 13 months (range: 0.1 – 41). Of patients who received Xgeva, 46% were female. Eighty-five percent were White, 5% Hispanic/Latino, 6% Asian, and 3% Black. The median age was 63 years (range: 18 – 93). Seventy-five percent of patients who received Xgeva received concomitant chemotherapy.

Table 1. Per-patient Incidence of Selecteda Adverse Reactions of Any Severity (Trials 1, 2, and 3)

CONFERENCE NEWS

Highlights From the 2015 Genitourinary Cancers Symposium

Reference

Conteduca V, Caffo O, Derosa L, et al. Metabolic syndrome in castration-resistent prostate cancer patients treated with abiraterone. J Clin Oncol. 2015;33(suppl 7):abstract 213. Poster presented at: 2015 Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL.

Obesity and Survival in Metastatic Renal Cell Carcinoma

Obesity typically has negative health

effects, including those related to cancer. Obesity and overweight are established risk factors for developing renal cell carcinoma (RCC) and other types of solid cancers. But a new study suggests that obesity and overweight have a paradoxical effect by improving survival once patients develop metastatic RCC. The study was based on more than 4000 patients with metastatic RCC who were enrolled in Pfizer-sponsored phase 2 and 3 clinical trials from 2003 to 2013. The impact of body mass index (BMI) was assessed on overall survival, progression-free survival, and overall response rate.

that several lines of evidence suggest that higher BMI may be associated with more indolent RCC. Data from The Cancer Genome Atlas suggest that fatty acid synthase (FASN) gene expression is associated with overall survival in RCC. In a multivariate analysis of the IMDC database (subjects in the current study), FASN staining was associated with prognosis but not overall survival.

Albiges noted that this finding was observed in clear cell RCC only. “We hypothesize that lipid metabolism may be modulated by the fat-laden tumor cells. FASN staining in the IMDC co-

Photo by © ASCO/Todd Buchanan 2015.

“These are preliminary results. Larger prospective trials are needed,” said Vincent Conteduca, MD, IRCCS, Istituto Scientifico Romagnola per lo Studio e la Cura del Tumori, Meldola, Italy. Although further study is needed, these findings may be important when selecting treatment, the authors said.

Androgen deprivation therapy is known to increase the risk of metabolic syndrome and cardiovascular disease (CVD). The authors of this study wanted to look at metabolic alterations related to treatment with abiraterone, a novel hormonal therapy, and determine the impact of metabolic syndrome on progression-free survival and overall survival.

The retrospective study included 178 consecutive men with metastatic CRPC treated with abiraterone 100 mg and prednisone 5 mg twice a day in 28-day cycles after failing on previous treatment with docetaxel. Patients were evaluated at baseline and every 3 months for the presence of metabolic syndrome and cardiovascular events, and CT scans were obtained every 3 months.

At baseline, 67 of 178 patients (37.6%) met the definition of metabolic syndrome established by the modified Adult Treatment Panel III, or ATP III. Eleven additional patients developed metabolic syndrome on treatment with abiraterone.

Median progression-free survival was 4.7 months for those with metabolic syndrome versus 9 months for those without it (P=.003).

The presence of metabolic syndrome was associated with a 71% increased risk of disease progression or all-cause death compared with no metabolic syndrome, Conteduca noted.

Median overall survival was 14.7 months for those with metabolic syndrome and 22.3 months for those without it, but this difference was not statistically significant (P=.340).

CVD was reported in 26 patients (14.6%): 15 of 111 without metabolic syndrome (13.5%) and 11 of 68 with metabolic syndrome (16.4%).

The presence of preexisting CVD risk factors did not affect cardiovascular events during abiraterone treatment.

Opening day at the 2015 Genitourinary Cancers Symposium.

In 4657 patients included in the International mRCC Database Consortium (IMDC) biospecimen data set, a higher BMI was associated with improved likelihood of survival, longer time to treatment failure, and greater tumor shrinkage compared with normal or lower BMI. Among these patients, 2828 (61%) met criteria for being obese or overweight (ie, BMI ≥25 kg/m2), and 1829 (39%) were of normal weight or underweight (BMI <25 kg/m2).

A high BMI was associated with extended survival versus a lower BMI: 23.4 months versus 14.5 months, respectively (P=.0008). In an adjusted analysis, this difference translated to a 17% reduction in risk for mortality among patients with a high BMI. Median progression-free survival was 8.2 months in those with high BMI versus 5.5 months in those with lower BMI, which translated to an 18% reduced risk of disease progression (P<.0001). Overall response rates to treatment were 25.3% versus 17.6%, respectively (P<.001).

Lead author Laurence Albiges, MD, PhD, a medical oncologist at the Institut Gustave Roussy, Paris, France, said

hort is ongoing to better investigate the obesity paradox in metastatic RCC,” she said.

When stratified by line of therapy, the results remained unchanged, but when analyzed according to histological subtype, the favorable outcomes associated with higher BMI remained true only in clear cell RCC. Reference

Albiges L, Hakimi AA, Lin X, et al. The impact of BMI on outcomes of patients with metastatic renal cell carcinoma treated with targeted therapy: an external validation data set and analysis of underlying biology from The Cancer Genome Atlas. J Clin Oncol. 2015;33(suppl 7):abstract 405. Poster presented at: 2015 Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL.

Radium-223 and Pain

Radium-223 is a novel alpha-emitting radiopharmaceutical that has been found to prolong lives of men with castration-resistant prostate cancer (CRPC) and bone metastasis. Results from the phase 3 ALSYMPCA trial showed that radium-223 prolonged overall survival by 2.8 months versus placebo (P<.001) and prolonged the time to first symptomatic skeletal event primarily associated with bone pain by

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5.8 months compared with placebo (P<.001).

Radium-223 also has potential to reduce the severity of pain associated with bone metastases and to improve enjoyment of life, as shown in the safety results of a US Expanded Access Program (US EAP, a multicenter, prospective interventional, open-label phase 2 trial) that was initiated to provide radium-223 to patients with CRPC and symptomatic bone metastases.

In the US EAP, treatment with radium-223 achieved pain relief in 43% of patients, 19% had no change in pain, 28% had worsening pain, and 10% had a mix of worsening and improved pain.

These findings were obtained in men not on opioids at baseline.

According to the authors, led by Michael Morris, MD, Memorial Sloan Kettering Cancer Center in New York City, the effect of radium-223 cannot be adequately interpreted in patients taking opioids at baseline due to the confounding effect of change in opioids after initiation of treatment.

Safety results were reported on 184 men with a median age of 70 years and median prostate-specific antigen (PSA) of 129 ng/mL; 59% received prior docetaxel, 10% were on current bisphosphonates, and 17% were on current denosumab. Of these men, 109 were not on opioids at baseline.

A significant improvement in pain severity (as assessed by mean pain score) was achieved by radium-223 treatment at all treatment visits (P<.05), which corresponded to a higher percentage of patients experiencing improvement versus worsening at each treatment visit. Among 97 patients with the potential for pain improvement at baseline (pain score ≥2), 57 (59%) experienced pain improvement during at least 1 on-treatment visit.

Radium-223 treatment was also associated with reduced pain interference in general activity, sleep, work, and walking, as well as with a higher percentage of patients who reported improved enjoyment of life.

Reference

Morris MJ, Sartor AO, Vogelzang NJ, et al. Effect of radium-223 dichloride (Ra-223) on pain from US EAP. J Clin Oncol. 2015;33(suppl 7):abstract 160. Poster presented at: 2015 Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL.

New Biomarker for Survival

Cumulative bone scan lesion area (BSLA) appears to be able to predict response to treatment and overall survival in patients with metastatic castration-resistant prostate cancer (CRPC).

These findings have been replicated with different drug treatments.

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MAY 2015 I VOL 8, NO 3

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CONFERENCE NEWS

Highlights From the 2015 Genitourinary Cancers Symposium Continued from page 13

Reference

Brown MS, Kim HJ, Chu GH, et al. Quantitative bone scan lesion area as an early surrogate outcome measure indicative of overall survival in metastatic castration-resistant prostate cancer. J Clin Oncol. 2015; 33(suppl 7):abstract 179. Poster presented at: 2015 ­ Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL.

Quality of Life in Long-Term Survivors of Bladder Cancer

A survey of survivors of muscleinvasive bladder cancer demonstrated that bladder-sparing trimodality therapy (TMT) was associated with improved quality of life (QOL) and bowel function compared with radical cystectomy (RC).

Radiation Oncology Program, Boston, Massachusetts. “Whether these significant findings translate into clinically meaningful differences requires further study.”

The cross-sectional, multi-institutional study compared long-term QOL in patients aged 18 years or older with nonmetastatic muscle invasive bladder

Photo by © ASCO/Todd Buchanan 2015.

BSLA is an imaging biomarker that is computed semi-automatically from whole-body scintigraphic imaging as a measure of overall bone tumor burden in CRPC. The present study sought to test BSLA in 198 anonymous patients with CRPC enrolled in a treatment trial (127 on treatment and 71 on placebo). This cohort of men was independent from other cohorts used to develop the biomarker and initial validation studies, and the current study used a drug with a different mechanism of action from previous trials, reported Matthew Brown, PhD, Professor of Radiology at the University of California Los Angeles.

Standard of care whole-body scintigraphy was performed at baseline and week 12. BSLA was calculated at both time points. A 30% increase in BSLA was defined as disease progression, and a 30% decrease in BSLA was defined as response.

In a multivariate Cox regression analysis, low baseline BSLA <2000 mm2 was a significant prognostic factor (P=.003) and predicted longer survival (P<.001) compared with high BSLA ≥2000 mm2.

Looking at BSLA as a surrogate marker of outcome, patients without progressive disease according to BSLA at week 12 had significantly longer overall survival compared with patients who had progressive disease at that time point (P=.007).

Opening day at the 2015 Genitourinary Cancers Symposium.

“Muscle-invasive bladder cancer can be treated with either muscle-sparing trimodality therapy or radical cystectomy. Both modalities are associated with 50% to 60% overall survival at 5 years.

Both TMT and RC provide good longterm outcomes in these patients, but our study suggests that TMT has some significant advantages,” said presenting author Kimberly S. Mak, MD, Harvard

cancer diagnosed between 1990 and 2011 who had been disease free for at least 2 years. A questionnaire was sent to 226 eligible patients and was returned by 173 patients, for a response rate of 77%. Instruments used to assess QOL included EuroQOL (EQ)-5D 3L and EQ VAS, EORTC QLQ-C30, and Expanded Prostate Cancer Index Composite (EPIC) – Bowel Domain.

Sixty-four patients were treated with TMT and 109 with RC. Of those treated with RC, 89 had an ileal conduit and 18 had neobladder diversions. Median time from diagnosis to questionnaire was 9 years for the TMT group and 6 years for the RC group.

When baseline characteristics were compared between the 2 treatment groups, no significant difference was observed for age at diagnosis, age at the time of responding to the questionnaire, gender, smoking status, clinical stage, or comorbidities.

In a univariate analysis, TMT was associated with better general QOL compared with RC, with a significant 4.8-point difference on the EQ-5D 3L Visual Analog Scale (P=.07) and a 7.4-point difference on the EORTC QLQ-C30 (P=.02).

In a multivariate analysis, adjusted for age, time from diagnosis, year of treatment, gender, and comorbidity status, TMT achieved significantly better general QOL by an average of 6 or 7 points (P=.005). Looking at bowel function on multivariate analysis, TMT achieved an average increment of 4.5 points compared with RC on the EPIC bowel function subscale. However, there was no difference between treatments on the EPIC bowel bother subscale. Both groups had similar urinary QOL, as assessed by the EORTC-QLQBLM30 instrument. n Reference

Mak KS, Smith A, Eidelman A, et al. Quality of life in long-term survivors of muscle-invasive bladder cancer. ­­J Clin Oncol. 2015;33(suppl 7):abstract 319. Poster presented at: 2015 Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL.

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GENETIC COUNSELING

Inherited Ovarian Cancer...

College of Obstetricians and Gynecologists recommend against ovarian cancer screening in the general population.3 For women at high risk who have elected not to proceed with risk-reducing surgery, transvaginal ultrasound with CA-125 levels can be considered every 6 months beginning at age 30 or 5 to 10 years earlier than the youngest age of ovarian cancer diagnosis in the family.4 Even in this population, however, available surveillance options have not been shown to decrease ovarian cancer morbidity or mortality.3 In fact, it has been suggested that providing women with the option of surveillance for ovarian cancer gives them false hope, and when surveillance is not offered, they are more likely to proceed with risk-reducing surgery.5 Although bilateral salpingo-oophorectomy is a proven ovarian cancer prevention strategy, it is also an invasive procedure, affects quality of life, and may have health hazards. Additionally, for bilateral salpingo-oophorectomy to be effective in high-risk women, they have to be identified, and the majority of women with inherited mutations do not know they have them.6 Moreover, as only 7% to 10% of ovarian cancer cases occur in mutation carriers, this would not be an effective public health strategy to reduce ovarian cancer mortality and morbidity.3 Therefore, additional surveillance and prevention options are needed.

Data have demonstrated that at least some high-grade serous carcinomas originate in the fallopian tube. Therefore, one suggestion is the option of bilateral salpingectomy in premenopausal, high-risk women and for all women at the time of routine gynecologic surgery.3 However, to determine the impact of this procedure in preventing ovarian cancer, the proportion of cancers arising in the fallopian tubes would need to be known. It would also need to be determined if there is a genotypic correlation, so that individuals receive appropriate genetic counseling. Presently, the only proven intervention is bilateral salpingo-oophorectomy. It is essential that new screening and imaging technologies be developed to improve the outcome and quality of life for women at high risk for ovarian cancer.

Due to the high mortality rate and lack of effective surveillance methods, identifying woman at increased risk for ovarian cancer is crucial, as it allows them to have the option of risk-reducing surgery. Historically, it was believed that 5% to 12% of invasive ovarian carcinomas were due to hereditary susceptibility.7 The two most common hereditary ovarian cancer syndromes were

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believed to be hereditary breast and ovarian cancer (HBOC) syndrome and Lynch syndrome. HBOC is associated with mutations in the BRCA1 and

Cristi Radford, MS, CGC

It has been suggested that providing women with the option of surveillance for ovarian cancer gives them false hope, and when surveillance is not offered, they are more likely to proceed with risk-reducing surgery.

BRCA2 genes, while Lynch syndrome is associated with mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes. As has been seen with other disease sites, the availability of multigene inherited cancer tests and their incorporation into clinical practice has altered the understanding of hereditary cancer, and this is also true for ovarian cancer.

Studies continue to demonstrate that BRCA1/2 account for the majority of known inherited epithelial ovarian cancer cases. However, multigene testing options have demonstrated that the remaining identifiable mutations represent a diverse spectrum, with Lynch syndrome typically representing a small percentage of known mutations. This was initially demonstrated in 2011 by Walsh and colleagues, who screened an unselected cohort of 360 women with primary ovarian, peritoneal, or fallopian tube carcinoma for mutations in 21 genes.8 Approximately 1 in 4 (82/360) women were found to carry a germline, loss-of-function mutation, and a total of 85 mutations were identified. BRCA1/2

represented 74% of mutations, whereas mutations in genes associated with Lynch syndrome only represented 2% of mutations. The remaining 24% of mutations were found in 9 genes, with the greatest proportion being CHEK2 (5/85) and BRIP1 (4/85). Since this study was undertaken, several others have reported on the results of inherited cancer panels in specific patient populations. The cohorts analyzed have included those that have particular age of onset and/or family history criteria, those that meet defined clinical criteria, and patient samples submitted to a specific genetic testing company.9 A laboratory cohort presented at the 2014 meeting of the American Society of Clinical Oncology reviewed the mutation spectrum of 263 patients diagnosed with ovarian cancer who were tested with a 25-gene inherited cancer panel. Again, BRCA1/2 accounted for over half the mutations identified (59.6%), and mutations in genes associated with Lynch syndrome represented 5.8%. The remaining 35% of mutations were represented by 8 genes, with the most mutations being identified in ATM, BRIP1, and NBN.10 A cohort from a different laboratory analyzed data for the contribution of 19 genes in a BRCA1/2-negative population of 911 patients with a personal history of breast and/or ovarian cancer. When the patients with breast cancer only were removed from the data set, 558 patients remained (466 with a personal history of ovarian cancer and 92 with a personal history of breast and ovarian cancer). In 41 of these individuals, 42 mutations were found. Unlike the other reported data sets, the most mutations were found to be in the Lynch syndrome genes, followed by BRIP1, CHEK2, and ATM. The common theme in all of these data sets is that a variety of genes have a role in ovarian cancer risk, and simply testing for BRCA1/2 or Lynch syndrome will miss a large percentage of cases.

In addition to the diverse spectrum of mutations found in genes associated with a moderate or high risk of ovarian cancer, multigene testing options have also uncovered expanded phenotypes.

In the Walsh article, none of the ovarian cancer patients found to have a mutation associated with Lynch syndrome or Li-Fraumeni syndrome had family histories consistent with the syndromes as currently described in the literature.8 Minion and colleagues also reported on individuals found to have germline mutations in Lynch syndrome genes that did not meet Lynch syndrome clinical criteria, as well as individuals meeting Lynch syndrome clinical criteria who were found to have mutations in other

genes associated with increased ovarian cancer risk.11 Therefore, if clinicians rely on a testing strategy that analyzed only genes associated with defined clinical criteria associated with a syndrome, they may miss an identifiable mutation.

Individuals with BRCA mutations start off with cells prone to problems repairing DNA, and PARP inhibitors make it even more difficult for tumor cells to correct themselves.

Many of the genes analyzed in the previously mentioned data sets are part of the homologous recombination (HR) pathway. Cells contain multiple types of DNA repair mechanisms, and one of these is HR, which helps repair DNA damage including single-stranded DNA, double-stranded DNA breaks, and DNA cross-links. Additionally, HR has a role with DNA replication forks. BRCA1/2 are involved in the repair of DNA double-strand breaks via HR, and studying genes in this pathway has uncovered other genes associated with breast and/ or ovarian cancer risk. As BRCA1/2 are involved in the repair of DNA double-strand breaks via HR, cells with BRCA1/2 mutations have a decreased ability to repair double-strand breaks.

Ovarian cancers that have impaired HR ability are more sensitive to poly (ADP-ribose) polymerase, or PARP, inhibitors. PARP inhibitors keep cells from repairing themselves once they have been damaged by chemotherapy.12 Individuals with BRCA mutations start off with cells prone to problems repairing DNA, and PARP inhibitors make it even more difficult for tumor cells to correct themselves. Knowledge of the molecular mechanisms of BRCA1/2 has now permitted therapeutic interventions. On December 19, 2014, the US Food and Drug Administration (FDA) announced the approval of the first PARP inhibitor, Lynparza (olaparib), for patients with germline BRCA1/2 mutations and ovarian cancer who have had 3 or more lines of chemotherapy.13 Additional studies are needed to determine if the use of PARP inhibitors would be beneficial in other genes in the BRCA pathway or in other cancer sites.

Continued on page 16

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GENETIC COUNSELING

Inherited Ovarian Cancer... Continued from page 15 Take-Home Points

• 1 in 4 ovarian cancers have an inherited, genetic component.

• Identifying individuals at high risk of developing ovarian cancer is essential so these women can be offered riskreducing procedures.

• As the only effective intervention is bilateral salpingo-oophorectomy— which is an invasive procedure, can result in surgical menopause, and possibly has adverse health effects— new imaging and screening technologies are needed to improve the out-

come and quality of life for women at high risk.

• Lynparza (olaparib) became the first FDA-approved PARP inhibitor for women with BRCA mutations who have ovarian, fallopian tube, or primary peritoneal cancer and have had

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≥3 lines of chemotherapy.

• In addition to preventive opportunities, genetic testing for inherited ovarian cancer now has therapeutic implications for high-risk women. n

References

1. National Cancer Institute website. SEER stat fact sheets: ovary cancer. http://seer.cancer.gov/statfacts/ html/ovary.html. Accessed March 19, 2015.

2. Antoniou A, Pharoah PD, Narod S, et al. Average risk of breast and ovarian cancer associated with BRCA1 and BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72(5):1117-1130.

3. Daly M, Dresher CW, Yates MS, et al. Salpingectomy as a means to reduce ovarian cancer risk. Cancer Prev Res (Phila). pii: canprevres.0293.2014. Published online: January 13, 2015.

4. National Comprehensive Cancer Network website.

NCCN Clinical Practice Guidelines in Oncology. Genetic/ familial high-risk assessment: breast and ovarian. Version 2.2014. http://www.nccn.org/professionals/physician _gls/pdf/genetics_screening.pdf. Accessed March 19, 2015.

5. van Driel CM, de Bock GH, Arts HJ, et al. Stopping ovarian cancer screening in BRCA1/2 mutation carriers: effects on risk management decisions & outcome of risk-reducing salpingo-oophorectomy specimens. Maturitas. 2015;80(3):318-322.

6. Lancaster JM, Powell CB, Chen LM, et al; SGO Clinical Practice Committee. Society of Gynecologic Oncology statement on risk assessment for inherited gynecologic cancer predispositions. Gynecol Oncol.

2015;136(1):3-7.

7. Pal T, Permuth-Wey J, Betts JA, et al. BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer. 2005;104(12):28072816.

8. Walsh T, Casadei S, Lee MK, et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci U S A. 2011;108(44):1803218037.

9. Kurian AW, Kingham KE, Ford JM. Next-generation sequencing for hereditary breast and gynecologic cancer risk assessment. Curr Opin Obstet Gynecol.

2015;27(1):23-33.

10. Langer LR, McCoy H, Moyes K, et al. A study of ovarian cancer patients tested with a 25-gene panel of hereditary cancer genes. J Clin Oncol. 2014;32:5(suppl).

Abstract 1511.

11. Minion LE, Dolinsky JS, Chase DM, et al. Hereditary predisposition to ovarian cancer, looking beyond BRCA1/BRCA2. Gynecol Oncol. 2015;137(1):86-92.

12. Lupo B, Trusolino L. Inhibition of poly(ADP-ribosyl)ation in cancer: old and new paradigms revisited.

Biochim Biophys Acta. 2014;1846(1):201-215.

13. FORCE website. FDA review of olaparib. http:// www.facingourrisk.org/our-role-and-impact/advocacy/ current-actions/FDA-review-of-olaparib.php. Accessed March 19, 2015.

HAVE YOU EVER WANTED TO WRITE AN ARTICLE FOR TON? We’re interested in articles about the everyday issues that affect nurses— everything from chemotherapy safe handling to supportive care for patients to challenging cases.

Contact editorial@greenhillhc.com for information. www.TheOncologyNurse.com

NUTRITION IN FOCUS

Helping a Loved One With Cancer Eat Better During Treatment and Adjusting to Life and Nutrition After Treatment Abby C. Sauer, MPH, RD Abbott Nutrition

Abby C. Sauer, MPH, RD

Eating Better During Treatment

When a loved one is going through treatment for cancer, the caregiver’s roles may be many and varied, from helping to get a second opinion and deciding about treatment, to talking with visitors, or trying to keep up the loved one’s spirits. Grocery shopping, making favorite meals, and taking the patient out to dinner at a favorite restaurant are probably on this list as well. However, during cancer treatment, the patient might not always feel like eating and might not want to eat the same foods he or she used to enjoy.

For example, one day the patient may eat with gusto but the next, a favorite food may taste unappealing. The caregiver should not take this personally, as this is all a normal part of the process and how cancer treatment can impact a patient’s appetites and eating habits.

The caregiver can do much to help the loved one eat better during this tough time, to start strong and stay strong through his or her cancer treatment. Many of the following tips may be useful as strategies to help the caregiver cope through this process as well.

• Have lots of food options available and be prepared for changes in the patient’s tastes, which can change from day to day. Some days he or she will not want favorite foods because they do not taste good; other times, he or she will be able to eat a dish that did not taste good just the day before.

• Have lots of easy and nutritious snacks ready so the patient can have something available to eat whenever he or she is ready and feels hungry.

Good options include individual packs of applesauce or pudding, baby

www.TheOncologyNurse.com

carrots, fresh fruit, yogurt, cheese cubes, peanut butter and crackers, half a sandwich, or an oral nutritional supplement like Ensure Complete.

• Be prepared for times when the patient is able to eat only one or two foods for a few days in a row, until particular side effects go away. Even if he or she cannot eat at all, still encourage plenty of fluids, like clear liquids and light soups.

• Try not to push the patient into eating and drinking, as this strategy most likely will not lead to the desired outcome. Instead, offer encouragement and gentle, nonjudgmental support without being overwhelming, which is much more helpful to the patient and less stressful for the caregiver.

• Talk to the patient about any needs and concerns, and about ideas that might work best. A caregiver’s willingness to be flexible and supportive, no matter what the situation, will help the patient feel more in control.

Also, the caregiver should actively listen to what the patient is saying, as listening is one of the best ways to show caring and concern.

• Gather information, ideas, and recipes. Knowledge is power, and it helps to be armed with the right information on the importance of nutrition during cancer treatment and ways to help. Find recipes for comfort foods or new foods that will fit with what the patient wants to eat.

• Accept a helping hand. If other family members and friends offer to assist with grocery shopping, cooking, and eating, accept their offer—the extra help and company will benefit both the caregiver and the patient.

For further information on how to care for a loved one with cancer, go to the National Cancer Institute website at www.cancer.gov or the American Cancer Society website at www.cancer.org.

Adjusting to Life and Nutrition After Treatment

As treatment ends, patients and caregivers enter a new phase. Until now, the caregiver has probably been focused on getting the patient through treatment, with little time alone to think about things and come to terms with the many changes that have occurred.

Putting their own feelings and needs on hold until treatment is over is what

most caregivers do.

Once treatment ends, most people want to put the cancer experience behind them. Still, many caregivers are not sure what to do next. It can be a time of mixed emotions—happiness and relief that treatment is over are to be expected, but at the same time, the full impact of what the caregiver has gone through with a loved one may start to set in.

It is important to remember that during this time, each person involved in the cancer experience tends to adjust at his or her own pace. Some people are able to resume their regular activities right away; others may need some extra time to recover. The patient may still be coping with the effects of treatment and adjusting to all the changes. There may be pressure for the caregiver or loved one to get back to the way things were before cancer. Yet it is important to know that for some, this can still be an emotional period. The cancer patient and the caregiver both need time to come to terms with what has happened and to figure out a “new normal.” This means getting back to living life, but in a way that is probably different from before.

During treatment, the caregiver took on many roles. He or she may have been in charge of numerous decisions, allowing the loved one to step back from decision making to stay focused on getting through treatment. Once it’s over, it is common for caregivers to feel confused and to have many questions, such as “How do I help my loved one now? Should I go back to work, or stay at home? When will my loved one be ready to take on former roles and responsibilities?” The answers to these questions vary with each person. Moving forward, the caregiver must try to be patient and take things one day at a time.

If the caregiver has been putting his or her own needs aside, this may be a good time to think about self-care. Having some down time to recharge mind and spirit can help a person cope.

Things caregivers may want to think about include: • Getting back to activities they enjoy • Finding new ways to connect with friends • Establishing a support group and finding ways others can help, and • Keeping the focus on nutrition even after cancer treatment ends

Successful Nutrition Planning After Cancer Treatment

Many times, the appetite and eating problems a patient experiences during cancer treatment go away after the treatment ends. Problems such as a sore throat or taste changes tend to resolve, and the patient’s ability and desire to eat come back. It is important for the caregiver to recognize that good nutrition remains important for the patient, and the caregiver, even after treatment ends. It is important that the patients eat well to regain weight, strength, and energy on the road to recovery. There are some simple strategies that can be followed to help a patient eat well after cancer treatment, including: • Try small, frequent meals and snacks throughout the day • Start with simple meals and snacks.

Do not try too many spicy, fried, or fatty foods until the patient can handle these foods.

• Incorporate lots of seasonal and fresh fruits and vegetables to entice the taste buds • Include whole grains, including breads, oats, and cereals • Try low-fat dairy foods such as milk, yogurt, and cheese • Be sure to drink plenty of fluids each day • Limit fat, salt, and sugar, and...

• Most importantly, learn how to enjoy food again!

If caregivers needs more help with their loved one’s nutrition, encourage them to work with a registered dietitian who can help provide individualized advice. A caregiver can find a local registered dietitian through the Academy of Nutrition and Dietetics at www.eat right.org.

The role of the caregiver during and after cancer treatment is critical. The caregiver tends to serve many roles— nurse, housecleaner, chauffeur, chef— but loved one is the most important role. The support the caregiver provides is priceless to the patient and his or her recovery. Helping the patient with nutrition and eating provides that simple support the patient needs to feel better and get through this journey. n

Disclosure Statement Abby C. Sauer works for Abbott Nutrition Research & Development.

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NAVIGATION

What Is a Navigator?

Sharon S. Gentry, RN, MSN, AOCN, CBCN

The following article is reprinted from our sister publication CONQUER, the magazine written exclusively for patients with cancer. We offer it in the hope that it will provide an additional support resource for your patients. For more from CONQUER, visit www.conquer-magazine.com.

Y

ou have just been diagnosed with cancer, and one of the first people you meet on your healthcare team is introduced as a navigator.

Sharon S. “A what?” you think.

Gentry, RN, “I need doctors, not MSN, AOCN, CBCN a GPS!” But over time, you will realize this person is a great guide.

Because they are positioned inside the healthcare system and know the ins and outs of that world, as well as the community around the system, navigators can be a great resource. According to the dictionary, a navigator is a person

Your navigator may have a clinical background, such as a nurse or social worker, or he or she may have health education training, such as a community health worker or lay navigator. who finds out how to get to a place: a person who navigates a ship, an airplane, or a device (such as a computer) that is used to plan or find the route to a place. This is also a concise description of the navigators who work in the

oncology healthcare system today.

Navigators can get you to where you need to go, and can describe the route or journey you will be traveling as a pa-

Task of a Navigator

What type of cancer do I have?

Are there different types of my cancer?

What are good Internet resources?

What tests/scans will be performed?

What is the treatment for my cancer (surgery, radiation therapy, chemotherapy, immunotherapy, other)?

What can I expect after surgery?

What can I expect after my first chemotherapy treatment?

What is radiation like?

What can I expect at the surgeon/medical oncologist/radiation visit?

Why am I being sent to a high-risk clinic?

What is a survivorship care plan?

What did the doctor mean by palliative care?

Provide emotional support for patients

Who can talk to my spouse/partner?

What do I tell my children?

How can I tell my parents?

Is there someone to discuss financial concerns?

Will I be able to work?

Is there a support group?

I do not feel comfortable in groups. Is there someone I can talk with?

I cannot grasp all that is happening to me; who can I talk with?

Assist patients with logistics, such as transportation, costs

Is there transportation assistance?

I live far away. Is there an affordable place to stay?

What are the directions to the appointment/test?

Is there an interpreter available for me/my family?

Can you help me with the copays?

I am overwhelmed with these insurance forms; can you help?

Who can stay with my elderly parents while I get care?

Who do I see about my short-term or long-term disability forms?

Is there child care available?

Can someone help me with a living will?

Advocate for the patient

I feel dissatisfied with my care; can you help me?

I did not have a good experience with a healthcare team member; can you help me?

I did not feel comfortable asking questions; what did the doctor mean?

Can you review my care plan with me?

My appointments conflict with my work schedule; can you help?

I am frustrated with this bill, because another one came from the same visit. Are they all bills?

Why do I have to wait so long for an appointment?

Utilize community resources

Is there free legal aid available?

Is there an agency to help with medications?

Can I get financial help in my community?

Are there people/groups that can help with transportation?

Can someone clean my house?

Are there other survivors I can talk with?

www.aonnonline.org

www.accc-cancer.org/resources/ patientnavigation.asp

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Questions for Your Navigator

Provide education on your cancer diagnosis

The following websites offer additional information on cancer navigators:

www.hpfreemanpni.org/resources/

ty health worker or lay navigator.

When you look at the tasks (see box) that many navigators perform, you can realize what questions or concerns you

Orient patients to the care Who do I need to see for care now? system Where do I go for care?

What type of doctors will I be seeing in the system?

Can I stay in my community for care?

Who is the expert in this field?

What are the contact numbers for my healthcare team?

Who do I call in the evenings and on weekends?

Can I ask my questions to the healthcare team electronically?

PATIENT RESOURCES

www.cancerpatientnavigation.org/ resources.html

tient. Your navigator may have a clinical background, such as a nurse or social worker, or he or she may have health education training, such as a communi-

www.TheOncologyNurse.com

NAVIGATION

Think of your navigator as a partner who is focused on your personalized, individual care. Be honest with your navigator, so he or she can make appropriate referrals to enhance your care.

may want to share with them that will help you better navigate your care.

Your navigator is knowledgeable

about cancer care, and the cancer care system. Navigators view the healthcare system through the eyes of the patient.

They are aware of the treatment you expect to get throughout your care, and the community resources that can support you and your family. Navigators communicate with your healthcare team and collaborate on your behalf to facilitate your best care.

Think of your navigator as a partner who is focused on your personalized, individual care. If navigators do not

know an answer, they can direct you to another team member. They have a defined role, and will transition you to other healthcare team members as needed. Be honest with your navigator, so he or she can make appropriate referrals to enhance your care.

One of my favorite quotes comes from an article in Patient Education and Counseling that summed up what patients thought about their experience with navigators: “Having a navigator as someone with personal knowledge of the participant’s overall life situation, while also having direct linkages as an ‘insider’ to the health-care system, helping them through administrative challenges, offering security, comfort, or peace of mind by simply knowing that the navigator was there as a resource, ‘checking in’ with calls or informal visits, were all described by participants as examples of ‘being there’ ” [Patient Educ Couns. 2010;80:241-247].

I hope you will embrace the care of a navigator in your cancer journey. n

PERSONALIZED MEDICINE

President Obama’s Bet on Personalized Medicine Edward Abrahams, PhD President, Personalized Medicine Coalition

The following article is reprinted from our sister publication Personalized Medicine in Oncology. We offer it to provide a perspective about the future of medical care. For more from the publication Personalized Medicine in Oncology, visit www.personalizedmedonc.com.

“I

want the country that eliminated polio and mapped the human genome to lead a new era of medicine, one that delivers the right treatment at the right time.” So said the president of the United States in his State of the Union Address on January 20, 2015.

By calling attention to the promise of personalized medicine, the president underlined what has been the central contention of the Personalized Medicine Coalition for a decade: linking therapy to diagnostics and thereby targeting the right treatment to the right patient at the right time will lead to a paradigm shift in modern medicine, improving outcomes while lowering overall costs.

To be sure, the road is long, opposition real, and the president’s proposed invest-

ment of $215 million in fiscal year 2016 relatively small, given the stakes and the opportunity.

But a closer look at the president’s Precision Medicine Initiative reveals its potentially transformative implications

It proposes creating, over time, a healthcare system that eschews one-size-fitsall, trial-and-error medicine in favor of a targeted approach that will deliver better results at a lower overall cost. for the future of medicine. Even if small and only for 1 year, if Congress approves, the new program will transform the nature of the biomedical research enterprise, a fact not unnoted by the White House, which calls the initiative “a bold new research effort to revolu-

tionize how we improve health and treat disease.”

In particular, the president wants to: • Add $70 million to the budget of the National Cancer Institute (NCI) to study the genetic factors that cause cancer • Add $10 million to the budget of the Food and Drug Administration (FDA) to develop new approaches for evaluating next-generation genetic tests • Add $5 million to the budget of the Office of the National Coordinator for Health Information Technology to support the development of interoperability standards and requirements that address privacy and enable secure exchange of data across systems • And, most importantly, add $130 million to the budget of the National Institutes of Health (NIH) to build a “voluntary national research cohort” of a million or more volunteers in order to better understand the etiology of health and disease.

According to the White House, “Most medical treatments,” as proponents of personalized medicine have argued for some time, “have been de-

signed for the ‘average patient.’ As a result...treatments can be very successful for some patients but not for others.”

Advised by NIH Director Francis Collins, MD, PhD, and NCI Director Harold Varmus, MD, the president is proposing that we embark on a new era of discovery and delivery that places the individual at the center of his or her healthcare. It proposes creating, over time, a healthcare system that eschews one-size-fits-all, trial-and-error medicine in favor of a targeted approach that will deliver better results at a lower overall cost.

What makes this vision possible and, in 2015, realistic, as Drs Collins and Varmus wrote in The New England Journal of Medicine for February 26, have been the creation of new methods of distinguishing among patients that include proteomics, metabolomics, genomics, and other molecular assays as well as computational tools that facilitate the development of largescale databases, which can be used for research.

As they note, significant progress has already been made in understanding and therefore treating cancer as a genetic disease. The proposed additional inContinued on page 22

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RENAL CANCER

No Role for Adjuvant Sorafenib or Sunitinib in Locally Advanced Kidney Cancer Phoebe Starr

patients might derive a treatment benefit from adjuvant sorafenib or sunitinib.

Study Details

ASSURE enrolled 1943 patients who

underwent complete resection and were categorized as intermediate risk or high risk for recurrence according to tumor size and grade and lymph node involvement. Treatment arms were well bal-

anced for type of kidney cancer, type of surgery, performance status, and risk of recurrence.

Patients were randomized in a 1:1:1 ratio to receive sorafenib (n=649), suni-

Register today for the Naomi B. Haas, MD

U

se of adjuvant sorafenib and sunitinib failed to extend disease-free survival (DFS) in patients with locally advanced kidney cancer at high risk of recurrence, according to initial results from the ASSURE study presented at the 2015 Genitourinary Cancers Symposium.

ASSURE is the first and largest study of adjuvant vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors in kidney cancer.

Adjuvant sorafenib and sunitinib failed to extend disease-free survival in patients with locally advanced kidney cancer at high risk of recurrence.

Both sorafenib and sunitinib are widely effective in metastatic kidney cancer, and the investigators of ASSURE hoped that the drugs would also provide benefit in the adjuvant setting. However, the findings of this randomized trial suggest that close observation should remain the standard of care, they said.

“No one could be more disappointed in these results than me, except for patients with kidney cancer. Even though these drugs provide benefit in the metastatic setting, they did not reduce disease recurrence in the adjuvant setting, while they did increase side effects,” said lead author Naomi B. Haas, MD, Abramson Cancer Center of the University of Pennsylvania, Philadelphia.

Haas said analysis of tumor specimens collected during the trial may provide some clues to whether specific subsets of

20

MAY 2015 I VOL 8, NO 3

OCTOBER 1– 4 • HYATT REGENCY ATLANTA • ATLANTA, GEORGIA Our highly popular Annual Navigation and Survivorship Conference provides oncology navigation professionals with the opportunity to gain timely, relevant knowledge that will benefit them in their career while enhancing the care that they provide their patients.

MEETING HIGHLIGHTS: Stimulating educational sessions addressing topics such as:

Navigators Exploring Xtra Tracks (NEXT) for all levels of experience

• Psychosocial care for cancer patients

Navigation-related research and outcomes (poster presentations and educational sessions)

• Commission on Cancer updates • Navigation and survivorship care planning • Strengthening navigation and survivorship programs • Providing patient support and guidance in the age of personalized cancer care • Genetic counseling

Tumor-specific and skills breakout sessions Continuing education units Celebratory events for survivors, caregivers, navigators and their healthcare team members Network and create relationships with peers and key thought leaders

WHO SHOULD ATTEND: Oncology nurse navigators

Administrators

Practice managers

Patient or non-clinically licensed oncology navigators

Case managers

Financial counselors

Oncology nurses and nurse practitioners

Oncologists

Oncology social workers

TRAVEL GRANT OPPORTUNITIES: Navigators who meet certain criteria can apply for a travel grant that will allow them to participate in AONN+ educational and networking events. Learn more or apply at AONNonline.org/travel-grant/

www.TheOncologyNurse.com

RENAL CANCER

tinib (n=647), or placebo (n=647) for 1 year. After 1322 patients were accrued, the starting doses of active drugs were lowered and titrated according to side effects, which reduced the rates of discontinuation in the experimental arms from about 26% for patients initiated at full doses to 14% for those started on reduced doses. Haas said that the dosing

adjustments could have relevance for reducing discontinuation of these drugs in other settings.

Interim analysis revealed similar rates of recurrence in all 3 groups (around 40%) and of DFS (5.6-5.7 years), the primary end point of the trial. Five-year DFS rates were 53.8% for sunitinib and 52.8% for sorafenib, which were similar

to the 55.8% seen in the placebo arm.

Overall survival was not significantly different between treatment arms and ranged from 77% to 81%.

Based on these interim findings, the Data Safety and Monitoring Committee recommended release of the results.

Both active drugs had side effects.

The most common grade ≥3 side effects

CONFERENCE CO- CHAIRS Lillie Shockney, RN, BS, MAS University Distinguished Service Associate Professor of Breast Cancer Administrative Director, The Johns Hopkins Breast Center

AONN+ is pleased to present two new initiatives this year!

Director, Cancer Survivorship Programs at the Sidney Kimmel Cancer Center at Johns Hopkins Associate Professor, JHU School of Medicine Departments of Surgery, Oncology & Gynecology and Obstetrics

A special one-day

Associate Professor, JHU School of Nursing, Baltimore, Maryland

Sharon Gentry, RN, MSN, AOCN, CBCN Breast Health Navigator Novant Health Derrick L. Davis Cancer Center Winston-Salem, NC

PATIENT NAVIGATION TRACK CHAIR Mandi Chapman Member of the AONN+ Leadership Council and Director, George Washington University Cancer Institute

PATIENT NAVIGATION TRACK specifically geared toward patient and non-clinically licensed oncology navigators (Saturday, October 3) Specific

MULTI-STAKEHOLDER SESSIONS in partnership with the Association for Oncology Practice Management (AOPM) focused on the team approach with oncologists and financial counselors

AWARDS AND RECOGNITION: The Hero of Hope Award™ honors a person with cancer who has demonstrated great strength, spirit, grace and compassion during their battle.

Learn more or nominate your hero at AONNonline.org/community/heroes-of-hope/

The Oncology Nurse Excellence (ONE) Award recognizes an oncology nurse for outstanding contribution to oncology nursing practice, patient care and education.

Learn more or submit a nomination at TheOncologyNurse.com/one-award

FEES: AONN+ Member:

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were hypertension (16% for both sorafenib and sunitinib, and 4% for placebo), hand-foot reaction (sorafenib 33%, sunitinib 14%, and placebo 1%), rash (15%, 2%, and 1%, respectively), and fatigue (7%, 17%, and 3%, respectively).

Final analysis of recurrence and survival will be presented in the future.

“The findings suggest that patients with locally advanced kidney cancer treated with surgery should not receive adjuvant sorafenib or sunitinib,” Haas noted.

Other adjuvant trials are ongoing in kidney cancer. These include a study of axitinib (a VEGF receptor inhibitor) and a study of everolimus (mTOR inhibitor).

All patients in the trial exceeded the 4.6-year DFS projected in the null hypothesis when the trial was designed, she added.

Other adjuvant trials are ongoing in kidney cancer. These include a study of axitinib (a VEGF receptor inhibitor) and a study of everolimus (mTOR inhibitor), both of which are accruing patients. Adjuvant trials of immunotherapy and other targeted approaches are being considered.

During a question-and-answer session following Haas’ presentation at a premeeting presscast, moderator Charles Ryan, MD, professor, University of California San Francisco School of Medicine, noted that some oncologists are using adjuvant VEGF therapy with no supportive evidence. In his view, the interim results of ASSURE provide convincing evidence against this practice.

“The fact that this is a negative trial in no way diminishes its importance.

Tyrosine kinase inhibitors may not be as effective as chemotherapy in the adjuvant treatment of solid tumors,” Ryan stated. “This study supports my current practice of not using these drugs in the adjuvant setting.” n

*early bird rates end 5/31/15

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Reference

Haas NB, Manola J, Uzzo RG, et al. Initial results from ASSURE (E2805): adjuvant sorafenib or sunitinib for unfavorable renal carcinoma, an ECOG-ACRIN-led, NCTN phase III trial. J Clin Oncol. 2015;33(suppl 7):abstract 403. Presented at: 2015 Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL.

MAY 2015 I VOL 8, NO 3

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PROSTATE CANCER

AR-V7 Predicts Chemotherapy Sensitivity in Metastatic Prostate Cancer Phoebe Starr

In Search of Biomarkers

Emmanuel S. Antonarakis, MBBCh

E

xperts are hopeful that the field of prostate cancer will soon be catching up to breast cancer and some other tumor types with regard to genomic markers. A study featured at the 2015 Genitourinary Cancers Symposium suggests that the androgen receptor (AR) abnormality known as AR-V7 will turn out to be a predictive marker to help in treatment selection for patients with metastatic castration-resistant prostate cancer (CRPC).1 The study showed that the presence of AR-V7 in circulating tumor cells was predictive of sensitivity to chemotherapy with the taxanes docetaxel and cabazitaxel in men with metastatic CRPC. A previous study by the same team of researchers published last year showed that patients whose circulating tumor cells harbored AR-V7 had primary resistance to AR-directed therapy with enzalutamide and abiraterone.2

Taken together, the studies suggest that patients who are AR-V7 positive should be offered chemotherapy with one of the taxanes instead of enzalutamide or abiraterone, whereas patients who are AR-V7 negative can be offered either type of therapy safely.

Lead investigator Emmanuel S. Antonarakis, MBBCh, assistant professor of oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, said, “We urgently need markers that predict which therapies are going to be effective, and which are not, in individual patients with prostate cancer. AR-V7 testing may be extremely valuable in guiding treatment decisions for men with hormone-resistant disease in the near future.”

Antonarakis noted that the findings related to AR-V7 need to be validated in a prospective multicenter trial.

No commercial test for AR-V7 is currently available. These researchers and other investigators are working on developing a CLIA-approved test for AR-V7.

No commercial test for AR-V7 is currently available. These researchers and other investigators are working on developing a CLIA (Clinical Laboratory Improvement Amendments)-approved test

for AR-V7, Antonarakis said.

“Taxanes may be more efficacious than AR-directed therapy in AR-V7– positive men,” Antonarakis stated. “We need to prospectively validate this marker for therapy selection. The utility of the test will be greater in positive patients, if confirmed, whereas the utility in AR-V7–negative patients is not so great.”

Study Details

The present study included 37 men with metastatic CRPC who were initiating chemotherapy with docetaxel or enzalutamide; 17 of 37 patients (46%) were found to be AR-V7 positive. In general, at least 33% of patients with CRPC are AR-V7 positive.

The primary end point of the study was the association between AR-V7 status and prostate-specific antigen (PSA) response rates; a ≥50% reduction in PSA from baseline was considered to be a positive PSA response to therapy.

Other end points were progression-free survival (PFS) as measured by PSA levels and by clinical or radiographic progression.

PSA responses were achieved in 41% of AR-V7–positive and 65% of AR-V7– negative patients. The median PSAbased PFS rates were comparable between these 2 groups: 4.5 months versus 6.2 months, respectively; the median PFS was also comparable: 5.1 months versus 6.9 months, respectively.

When the investigators incorporated data from their previous study of 62 men who received abiraterone or enzalutamide, clinical outcomes were superior in AR-V7–positive men who received taxanes versus abiraterone or

enzalutamide, whereas outcomes were not significantly different for AR-V7– negative men who received either type of therapy.

A striking difference in PSA response was observed between the 2 types of therapy in AR-V7–positive men; 41% of patients showed positive response with the taxanes versus 0% (P<.001) with enzalutamide or abiraterone.

The median PSA-based PFS and the median PFS were significantly longer in AR-V7–positive men who received taxanes (P=.001 and P=.003, respectively).

“The AR-V7 biomarker is better at separating patients requiring AR-directed therapy versus chemotherapy. If a patient is AR-V7 positive, he has a greater chance of progression on enzalutamide or abiraterone compared with taxanes. In fact, he has a 79% lower chance of progression on a taxane and a 4.8-fold greater increase in risk of progression on enzalutamide or abiraterone,” Antonarakis commented. “In AR-V7–negative patients, there is no difference in PFS between taxanes or AR-directed therapy.”

According to these results, the presence of AR-V7 in circulating tumor cells is not associated with primary resistance to the taxanes; it is, however, associated with primary resistance to AR-directed therapy. n

References

1. Antonarakis ES, Lu C, Chen Y, et al. AR splice variant 7 (AR-V7) and response to taxanes in men with metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2015;33(suppl 7):abstract 138.

Presented at: 2015 Genitourinary Cancers Symposium; February 26-28, 2015; Orlando, FL. 2. Antonarakis ES, Lu C, Wang H, et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med. 2014;371(11):1028-1038

PERSONALIZED MEDICINE

President Obama’s Bet... Continued from page 19 vestment in cancer research builds on ongoing success in developing targeted treatments.

With the declining cost of sequencing and the increased ability to integrate multipanel arrays to produce clearer and more informed analyses, diagnostics are becoming more sophisticated and important in the practice of medicine. Increasing investment, therefore, in regulatory science will help allow the FDA to keep up with a rapid-

22

MAY 2015 I VOL 8, NO 3

ly evolving field and thereby ensure that the new tests coming on the market are accurate and reliable.

Aggregating data from multiple sources provides a foundation for personalized medicine. Therefore, it also makes sense to invest in ensuring that those data can cross systems to inform treatment, as the president proposes.

But most importantly for the future of biomedical research is the proposed creation of, in Drs Collins and Varmus’

words, “a longitudinal ‘cohort’ of 1 million or more Americans who have volunteered to participate in research.” By collecting biological specimens, including DNA, combining them with environmental information, and linking the data to electronic medical records, researchers will finally have the instrument they need to understand individual variation. They will be able to ask the right questions and derive sophisticated answers that will produce individual-

ized, and therefore more effective, treatments in the future.

Together, these 4 integrated programs put the federal government’s research agenda squarely on the side of finding the right treatment for the right patient at the right time. As the president said, “Something called precision medicine (in some cases, people call it personalized medicine) gives us one of the greatest opportunities for new medical breakthroughs that we have ever seen.” n www.TheOncologyNurse.com

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3RD ANNUAL

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FIRST ISSUE IN A 5-PART SERIES

A 5-part series The publishers of The Oncology Nurse-APN/PA are proud to present our 3rd annual Conquering the Cancer Care Continuum™ series.

THIRD ANNUAL

Conquering the Cancer Care Continuum Conquering Cancer Carthe i e Cont in SECoN

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Upcoming topics include: • Good Manufacturing Practice

Good Manufacturing Practice Lillie D. Shockney, RN, BS, MAS

University Distinguished Service Associate Professor of Breast Cancer Johns Hopkins University School of Medicine, Baltimore, MD

am very excited to announce our Conquering the Cancer Care Continuum series. these t publications will continue to address

RT SERIES E IN A 5-PA THIRD ISSU N UA L AN D IR TH

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Access to Qualit y Care

Lillie D. Sho ckney, RN University , BS,

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