TOP August 2014 by The Oncology Pharmacist

August 2014

www.TheOncologyPharmacist.com

Vol 7, No 3

Oncology Pharmacy Safety

Cancer Center Profile

Sequoia Regional Cancer Center, Kaweah Delta Health Care District

This is the fourth and final article in a series of articles that discuss issues related to hazardous materials in the workplace.

Chemotherapy: Current and Emerging Issues in Safe Handling of Antineoplastic and Other Hazardous Drugs Christine Roussel, PharmD, BCOP Clinical Pharmacy Manager, Doylestown Hospital Pharmacy Thomas H. Connor, PhD Research Biologist, National Institute for Occupational Safety and Health

T The pharmacy staff involved in pain management at the Kaweah Delta Health Care District (left to right): Clint Brown, PharmD; Yleana Garcia, PharmD, BCPS; and Richard Poirier, PharmD.

he Sequoia Regional Cancer Center is part of the Kaweah Delta Health Care District. It is located in Visalia, in the heart of California’s Central Valley. The cancer center offers a multidisciplinary approach to cancer care with a team of specialists who collaborate on helping patients navigate their cancer journey through diagnosis, treatment, and recovery. The combined efforts of the multidisciplinary team allow for the treatment of cancer utilizing all oncology specialties, ensuring the best care possible is available for each patient. Continued on page 20

Conference News

Highlights of the 2014 Annual Meeting of the American Society of Clinical Oncology

his is the last article of a 4-part series on the toxic effects and safe handling of hazardous drugs by Roussel and Connor.1-3 The previous 3 articles have covered the adverse health

provided a wealth of learning opportunities. Below are some highlights of the many ASCO presentations. These highlights touch upon the potentially practice-changing use of exemestane to treat breast cancer patients, preservation of fertility in premenopausal breast cancer survivors, and a study that shows that loratadine is not effective in treating pegfilgrastim-induced bone pain.

Continued on page 8

Best Practices

Positive Patient Outcomes Observed With a PharmacistPhysician Collaboration in a Palliative Care Outpatient Practice Meg Barbor

ositive patient outcomes, including a decrease in pain and constipation, were reported as a result of a pharmacist-physician collaboration in a palliative care outpatient practice. “With continued follow-up visits, the

patients in the study cohort sustained a 30% decrease in pain score,” according to Joseph D. Ma, PharmD. Researchers from the Skaggs School of Pharmacy and Pharmaceutical Sciences Continued on page 16

inside

Alice Goodman

his year, the American Society of Clinical Oncology (ASCO) celebrates the 50th anniversary of its founding. ASCO’s 2014 annual meeting acknowledged the society’s role in the advances made against cancer and presented the latest research and educational information about prevention, detection, and treatment of cancer. This year’s meeting was well attended and

effects of hazardous drugs, contamination of the workplace, and biomarkers of effect and exposure. The present article addresses several emerging issues that healthcare

Conference News: AVBCC. . Worksite Pharmacy Can Enhance Overall Drug Management of Patients With Cancer Conference News: ASCO Exemestane Plus Ovarian Suppression a Valid Option in Premenopausal Early Breast Cancer. . . . . . . . . . . . . . . . . . . . . . .

Loratadine and Bone Pain . . . . . . . .

Goserelin Preserves Ovarian Function in Premenopausal Women With Breast Cancer . . . . . .

Noteworthy Numbers. . . . Health Literacy

Now FDA Approved For patients with advanced gastric or gastroesophageal (GE) junction adenocarcinoma who have progressed after prior fluoropyrimidine- or platinum-containing chemotherapy, CYRAMZA is the only FDA-approved antiangiogenic to significantly extend overall survival CYRAMZA as a single agent is indicated for the treatment of patients with advanced or metastatic gastric or GE junction adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy.

IMPORTANT SAFETY INFORMATION FOR CYRAMZA WARNING: HEMORRHAGE CYRAMZA increased the risk of hemorrhage, including severe and sometimes fatal hemorrhagic events. Permanently discontinue CYRAMZA in patients who experience severe bleeding.

Warnings and Precautions Hemorrhage • CYRAMZA increased the risk of hemorrhage, including severe and sometimes fatal hemorrhagic events. In Study 1, which evaluated CYRAMZA as a single agent in advanced gastric cancer, the incidence of severe bleeding was 3.4% for CYRAMZA and 2.6% for placebo. Patients with gastric cancer receiving nonsteroid anti-inflammatory drugs (NSAIDs) were excluded from enrollment in Study 1; therefore, the risk of gastric hemorrhage in CYRAMZA-treated patients with gastric tumors receiving NSAIDs is unknown. Permanently discontinue CYRAMZA in patients who experience severe bleeding. Arterial Thromboembolic Events • Serious, sometimes fatal, arterial thromboembolic events (ATEs) including myocardial infarction, cardiac arrest, cerebrovascular accident, and cerebral ischemia occurred in clinical trials including 1.7% of 236 patients who received CYRAMZA as a single agent for gastric cancer in Study 1. Permanently discontinue CYRAMZA in patients who experience a severe ATE. Hypertension • An increased incidence of severe hypertension occurred in patients receiving CYRAMZA as a single agent (8%) as compared to placebo (3%). Control hypertension prior to initiating treatment with CYRAMZA. Monitor blood pressure every 2 weeks or more frequently as indicated during treatment. Temporarily suspend CYRAMZA for severe hypertension until medically controlled. Permanently discontinue CYRAMZA if medically significant hypertension cannot be controlled with antihypertensive therapy or in patients with hypertensive crisis or hypertensive encephalopathy. Infusion-Related Reactions • Prior to the institution of premedication recommendations across clinical trials of CYRAMZA, infusion-related reactions (IRRs) occurred

in 6 out of 37 patients (16%), including 2 severe events. The majority of IRRs across trials occurred during or following a first or second CYRAMZA infusion. Symptoms of IRRs included rigors/tremors, back pain/spasms, chest pain and/or tightness, chills, flushing, dyspnea, wheezing, hypoxia, and paresthesia. In severe cases, symptoms included bronchospasm, supraventricular tachycardia, and hypotension. Monitor patients during the infusion for signs and symptoms of IRRs in a setting with available resuscitation equipment. Immediately and permanently discontinue CYRAMZA for Grade 3 or 4 IRRs. Gastrointestinal Perforations • CYRAMZA is an antiangiogenic therapy that can increase the risk of gastrointestinal perforation, a potentially fatal event. Four of 570 patients (0.7%) who received CYRAMZA as a single agent in clinical trials experienced gastrointestinal perforation. Permanently discontinue CYRAMZA in patients who experience a gastrointestinal perforation. Impaired Wound Healing • CYRAMZA has not been studied in patients with serious or nonhealing wounds. CYRAMZA is an antiangiogenic therapy with the potential to adversely affect wound healing. Withhold CYRAMZA prior to surgery. Resume CYRAMZA following the surgical intervention based on clinical judgment of adequate wound healing. If a patient develops wound healing complications during therapy, discontinue CYRAMZA until the wound is fully healed. Clinical Deterioration in Child-Pugh B or C Cirrhosis • Clinical deterioration, manifested by new onset or worsening encephalopathy, ascites, or hepatorenal syndrome, was reported in patients with Child-Pugh B or C cirrhosis who received single-agent CYRAMZA. Use CYRAMZA in patients with Child-Pugh B or C cirrhosis only if the potential benefits of treatment are judged to outweigh the risks of clinical deterioration. Reversible Posterior Leukoencephalopathy Syndrome (RPLS) • RPLS has been reported at a rate of <0.1% in clinical studies with CYRAMZA. Confirm the diagnosis of RPLS with MRI and discontinue CYRAMZA in patients who develop RPLS. Symptoms may resolve or improve within days, although some patients with RPLS can experience ongoing neurologic sequelae or death.

CYRAMZA monotherapy significantly extended overall survival (OS)1

CYRAMZA significantly improved progression-free survival (PFS)1 MAJOR OUTCOME MEASURE

OS PROBABILITY

OVERALL SURVIVAL: MEDIAN – MONTHS (95% CI)1 1.0

CYRAMZA

Placebo

0.8

months

(4.4, 5.7)

(2.8, 4.7)

5.2

0.6

The phase III REGARD trial evaluated the efficacy and safety of CYRAMZA vs placebo in patients with locally advanced or metastatic gastric or GE junction adenocarcinoma who had progressed on or after prior fluoropyrimidine- or platinumcontaining chemotherapy. Major efficacy outcome measure was overall survival. Supportive efficacy outcome measure was progression-free survival. All patients were ECOG PS 0 or 1. Prior to enrollment, 85% of patients had progressed during treatment or within 4 months after the last dose of first-line chemotherapy for metastatic disease, and 15% of patients progressed during treatment or within 6 months after the last dose of adjuvant chemotherapy. Patients were randomized 2:1 to CYRAMZA 8 mg/kg q2w + BSC (n=238) or placebo + BSC (n=117).1

3.8

Hazard Ratio=0.78 (0.60, 0.998); P=0.047

0.4

CYRAMZA Placebo

0.2

0.0 0

238 117

10 11 12 13

14 15 16 17 18 19

0 1

0 0

TIME FROM RANDOMIZATION (MONTHS)

Number at Risk CYRAMZA Placebo

154 66

92 34

49 20

17 7

7 4

3 2

37%

• Median PFS with CYRAMZA was 2.1 months (95% CI: 1.5, 2.7) vs 1.3 months (95% CI: 1.3, 1.4) with placebo (hazard ratio 0.48 [95% CI: 0.38, 0.62]; P<0.001)1

CI=confidence interval; ECOG=Eastern Cooperative Oncology Group; PS=performance status; BSC=best supportive care.

INCREASE IN MEDIAN OS

Most Common Adverse Reactions

Use in Specific Populations

• The most commonly reported adverse reactions (all grades) occurring in ≥5% of patients receiving CYRAMZA and ≥2% higher than placebo in Study 1 were hypertension (16% vs 8%), diarrhea (14% vs 9%), headache (9% vs 3%), and hyponatremia (6% vs 2%).

• Pregnancy Category C: Based on its mechanism of action, CYRAMZA may cause fetal harm. Advise females of reproductive potential to avoid getting pregnant, including use of adequate contraception, while receiving CYRAMZA and for at least 3 months after the last dose of CYRAMZA. Animal models link angiogenesis, VEGF and VEGF Receptor 2 to critical aspects of female reproduction, embryofetal development, and postnatal development. There are no adequate or well-controlled studies of ramucirumab in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to a fetus.

• The most common serious adverse events with CYRAMZA in Study 1 were anemia (3.8%) and intestinal obstruction (2.1%). Red blood cell transfusions were given to 11% of CYRAMZA-treated patients vs 8.7% of patients who received placebo. • Clinically relevant adverse reactions reported in ≥1% and <5% of CYRAMZA-treated patients in Study 1 were: neutropenia (4.7% vs 0.9%), epistaxis (4.7% vs 0.9%), rash (4.2% vs 1.7%), intestinal obstruction (2.1% vs 0%), and arterial thromboembolic events (1.7% vs 0%). • Across clinical trials of CYRAMZA administered as a single agent, clinically relevant adverse reactions (including Grade ≥3) reported in CYRAMZA-treated patients included proteinuria, gastrointestinal perforation, and infusion-related reactions. In Study 1, according to laboratory assessment, 8% of CYRAMZA-treated patients developed proteinuria vs 3% of placebo-treated patients. Two patients discontinued CYRAMZA due to proteinuria. The rate of gastrointestinal perforation in Study 1 was 0.8% and the rate of infusion-related reactions was 0.4%. • As with all therapeutic proteins, there is the potential for immunogenicity. In clinical trials, 33/443 (7.4%) CYRAMZA-treated patients with post-baseline serum samples tested positive for antiramucirumab antibodies using an enzyme-linked immunosorbent assay (ELISA). However, this assay has limitations in detecting antiramucirumab antibodies in the presence of ramucirumab; therefore, the incidence of antibody development may not have been reliably determined. Neutralizing antibodies were detected in 1 of the 33 patients who tested positive for anti-ramucirumab antibodies.

• Nursing Mothers: It is recommended to discontinue nursing or discontinue CYRAMZA due to the potential risks to the nursing infant. • Females of Reproductive Potential: Advise females of reproductive potential that CYRAMZA may impair fertility. Please see Brief Summary of Prescribing Information for CYRAMZA, including Boxed Warning for hemorrhage, on next page. RB HCP ISI 21APR2014 Reference: 1. CYRAMZA (ramucirumab) [package insert]. Indianapolis, IN: Eli Lilly and Company; 2014. RB89001 05/2014 PRINTED IN USA © Lilly USA, LLC 2014. ALL RIGHTS RESERVED. CYRAMZA™ is a trademark of Eli Lilly and Company.

Visit CYRAMZANowApproved.com

Drug Interactions • No formal drug interaction studies have been conducted.

www.TheOncologyPharmacist.com

August 2014 I VOL 7, NO 3

CYRAMZATM (ramucirumab) injection BRIEF SUMMARY: For complete safety, please consult the full Prescribing Information. WARNING: HEMORRHAGE CYRAMZA increased the risk of hemorrhage, including severe and sometimes fatal hemorrhagic events. Permanently discontinue CYRAMZA in patients who experience severe bleeding. INDICATIONS AND USAGE CYRAMZA as a single-agent is indicated for the treatment of patients with advanced or metastatic, gastric or gastroesophageal junction adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy. CONTRAINDICATIONS None. WARNINGS AND PRECAUTIONS Hemorrhage CYRAMZA increased the risk of hemorrhage, including severe and sometimes fatal hemorrhagic events. In Study 1, the incidence of severe bleeding was 3.4% for CYRAMZA and 2.6% for placebo. Patients with gastric cancer receiving non-steroid anti-inflammatory drugs (NSAIDs) were excluded from enrollment in Study 1; therefore, the risk of gastric hemorrhage in CYRAMZA-treated patients with gastric tumors receiving NSAIDs is unknown. Permanently discontinue CYRAMZA in patients who experience severe bleeding. Arterial Thromboembolic Events Serious, sometimes fatal, arterial thromboembolic events (ATEs) including myocardial infarction, cardiac arrest, cerebrovascular accident, and cerebral ischemia occurred in clinical trials including 1.7% of 236 patients who received CYRAMZA as a single agent for gastric cancer in Study 1. Permanently discontinue CYRAMZA in patients who experience a severe ATE. Hypertension An increased incidence of severe hypertension occurred in patients receiving CYRAMZA as a single agent (8%) as compared to placebo (3%). Control hypertension prior to initiating treatment with CYRAMZA. Monitor blood pressure every two weeks or more frequently as indicated during treatment. Temporarily suspend CYRAMZA for severe hypertension until medically controlled. Permanently discontinue CYRAMZA if medically significant hypertension cannot be controlled with antihypertensive therapy or in patients with hypertensive crisis or hypertensive encephalopathy. Infusion Related Reactions Prior to the institution of premedication recommendations across clinical trials of CYRAMZA, infusion related reactions (IRRs) occurred in 6 out of 37 patients (16%), including two severe events. The majority of IRRs across trials occurred during or following a first or second CYRAMZA infusion. Symptoms of IRRs included rigors/tremors, back pain/spasms, chest pain and/or tightness, chills, flushing, dyspnea, wheezing, hypoxia, and paresthesia. In severe cases, symptoms included bronchospasm, supraventricular tachycardia, and hypotension. Monitor patients during the infusion for signs and symptoms of IRRs in a setting with available resuscitation equipment. Immediately and permanently discontinue CYRAMZA for Grade 3 or 4 IRRs. Gastrointestinal Perforations CYRAMZA is an antiangiogenic therapy that can increase the risk of gastrointestinal perforation, a potentially fatal event. Four of 570 patients (0.7%) who received CYRAMZA as a single-agent in clinical trials experienced gastrointestinal perforation. Permanently discontinue CYRAMZA in patients who experience a gastrointestinal perforation. Impaired Wound Healing CYRAMZA has not been studied in patients with serious or non-healing wounds. CYRAMZA is an antiangiogenic therapy with the potential to adversely affect wound healing. Withhold CYRAMZA prior to surgery. Resume following the surgical intervention based on clinical judgment of adequate wound healing. If a patient develops wound healing complications during therapy, discontinue CYRAMZA until the wound is fully healed. Clinical Deterioration in Patients with Child-Pugh B or C Cirrhosis Clinical deterioration, manifested by new onset or worsening encephalopathy, ascites, or hepatorenal syndrome was reported in patients with Child-Pugh B or C cirrhosis who received single-agent CYRAMZA. Use CYRAMZA in patients with Child-Pugh B or C cirrhosis only if the potential benefits of treatment are judged to outweigh the risks of clinical deterioration. Reversible Posterior Leukoencephalopathy Syndrome (RPLS) RPLS has been reported with a rate of <0.1% in clinical studies with CYRAMZA. Confirm the diagnosis of RPLS with MRI and discontinue CYRAMZA in patients who develop RPLS. Symptoms may resolve or improve within days, although some patients with RPLS can experience ongoing neurologic sequelae or death. ADVERSE REACTIONS 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 practice. In Study 1, the most common adverse reactions (all grades) observed in CYRAMZA-treated patients at a rate of ≥10% and ≥2% higher than placebo were hypertension and diarrhea. The most common serious adverse events with CYRAMZA were anemia (3.8%) and intestinal obstruction (2.1%). Red blood cell transfusions were given to 11% of CYRAMZA-treated patients versus 8.7% of patients who received placebo. Table 1: Adverse Reactions Occurring at Incidence Rate ≥5% and a ≥2% Difference Between Arms in Patients Receiving CYRAMZA in Study 1 CYRAMZA (8 mg/kg) Placebo Adverse Reactions N=236 N=115 (MedDRA)a All Grades Grade 3-4 All Grades Grade 3-4 System Organ Class (Frequency %) (Frequency %) (Frequency %) (Frequency %) Gastrointestinal Disorders Diarrhea 14 1 9 2 Metabolism and Nutrition Disorders Hyponatremia 6 3 2 1 Nervous System Disorders Headache 9 0 3 0 Vascular Disorders Hypertension 16 8 8 3 a MedDRA Version 15.0.

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C Risk Summary Based on its mechanism of action, CYRAMZA may cause fetal harm. Animal models link angiogenesis, VEGF and VEGF Receptor 2 to critical aspects of female reproduction, embryofetal development, and postnatal development. There are no adequate or well controlled studies of ramucirumab in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to a fetus. Animal Data No animal studies have been specifically conducted to evaluate the effect of ramucirumab on reproduction and fetal development. In mice, loss of the VEGFR2 gene resulted in embryofetal death and these fetuses lacked organized blood vessels and blood islands in the yolk sac. In other models, VEGFR2 signaling was associated with development and maintenance of endometrial and placental vascular function, successful blastocyst implantation, maternal and feto-placental vascular differentiation, and development during early pregnancy in rodents and non-human primates. Disruption of VEGF signaling has also been associated with developmental anomalies including poor development of the cranial region, forelimbs, forebrain, heart, and blood vessels. Nursing Mothers It is not known whether CYRAMZA is excreted in human milk. No studies have been conducted to assess CYRAMZA’s impact on milk production or its presence in breast milk. Human IgG is excreted in human milk, but published data suggests that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. Because many drugs are excreted in human milk and because of the potential risk for serious adverse reactions in nursing infants from ramucirumab, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use The safety and effectiveness of CYRAMZA in pediatric patients have not been established. In animal studies, effects on epiphyseal growth plates were identified. In cynomolgus monkeys, anatomical pathology revealed adverse effects on the epiphyseal growth plate (thickening and osteochondropathy) at all doses tested (5-50 mg/kg). Ramucirumab exposure at the lowest weekly dose tested in the cynomolgus monkey was 0.2 times the exposure in humans at the recommended dose of ramucirumab as a single-agent. Geriatric Use Clinical Trials of CYRAMZA as a single agent did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Of the 236 patients who received CYRAMZA in Study 1, 35% were 65 and over, while 9% were 75 and over. Renal Impairment No dedicated clinical studies have been conducted to evaluate the effect of renal impairment on the pharmacokinetics of ramucirumab. Hepatic Impairment No dedicated clinical studies have been conducted to evaluate the effect of hepatic impairment on the pharmacokinetics of ramucirumab. Females and Males of Reproductive Potential Fertility Advise females of reproductive potential that CYRAMZA may impair fertility. Contraception Based on its mechanism of action, CYRAMZA may cause fetal harm. Advise females of reproductive potential to avoid getting pregnant while receiving CYRAMZA and for at least 3 months after the last dose of CYRAMZA. DOSAGE AND ADMINISTRATION Recommended Dose and Schedule The recommended dose of CYRAMZA is 8 mg/kg every 2 weeks administered as an intravenous infusion over 60 minutes. Continue CYRAMZA until disease progression or unacceptable toxicity. Do not administer CYRAMZA as an intravenous push or bolus. Premedication Prior to each CYRAMZA infusion, premedicate all patients with an intravenous histamine H1 antagonist (e.g., diphenhydramine hydrochloride). For patients who have experienced a Grade 1 or 2 infusion reaction, also premedicate with dexamethasone (or equivalent) and acetaminophen prior to each CYRAMZA infusion. Dose Modifications Infusion Related Reactions (IRR) • Reduce the infusion rate of CYRAMZA by 50% for Grade 1 or 2 IRRs. • Permanently discontinue CYRAMZA for Grade 3 or 4 IRRs. Hypertension • Interrupt CYRAMZA for severe hypertension until controlled with medical management. • Permanently discontinue CYRAMZA for severe hypertension that cannot be controlled with antihypertensive therapy. Proteinuria • Interrupt CYRAMZA for urine protein levels ≥2 g/24 hours. Reinitiate treatment at a reduced dose of 6 mg/kg every 2 weeks once the urine protein level returns to <2 g/24 hours. If the protein level ≥2 g/24 hours reoccurs, interrupt CYRAMZA and reduce the dose to 5 mg/kg every 2 weeks once the urine protein level returns to <2 g/24 hours. • Permanently discontinue CYRAMZA for urine protein level >3 g/24 hours or in the setting of nephrotic syndrome. Wound Healing Complications • Interrupt CYRAMZA prior to scheduled surgery until the wound is fully healed. Arterial Thromboembolic Events, Gastrointestinal Perforation, or Grade 3 or 4 Bleeding • Permanently discontinue CYRAMZA PATIENT COUNSELING INFORMATION Advise patients: • That CYRAMZA can cause severe bleeding. Advise patients to contact their health care provider for bleeding or symptoms of bleeding including lightheadedness. • Of increased risk of an arterial thromboembolic event. • To undergo routine blood pressure monitoring and to contact their health care provider if blood pressure is elevated or if symptoms from hypertension occur including severe headache, lightheadedness, or neurologic symptoms. • To notify their health care provider for severe diarrhea, vomiting, or severe abdominal pain. • That CYRAMZA has the potential to impair wound healing. Instruct patients not to undergo surgery without first discussing this potential risk with their health care provider. • Of the potential risk for maintaining pregnancy, risk to the fetus, or risk to postnatal development during and following treatment with CYRAMZA and the need to avoid getting pregnant, including use of adequate contraception, for at least 3 months following the last dose of CYRAMZA. • To discontinue nursing during CYRAMZA treatment. Additional information can be found at www.CYRAMZAhcp.com.

Clinically relevant adverse reactions reported in ≥1% and <5% of CYRAMZA-treated patients in Study 1 were: neutropenia (4.7% CYRAMZA versus 0.9% placebo), epistaxis (4.7% CYRAMZA versus 0.9% placebo), rash (4.2% CYRAMZA versus 1.7% placebo), intestinal obstruction (2.1% CYRAMZA versus 0% placebo), and arterial thromboembolic events (1.7% CYRAMZA versus 0% placebo). Across clinical trials of CYRAMZA administered as a single agent, clinically relevant adverse reactions (including Grade ≥3) reported in CYRAMZA-treated patients included proteinuria, gastrointestinal perforation, and infusion-related reactions. In Study 1, according to laboratory assessment, 8% of CYRAMZA–treated patients developed proteinuria versus 3% of placebo-treated patients. Two patients discontinued CYRAMZA due to proteinuria. The rate of gastrointestinal perforation in Study 1 was 0.8% and the rate of infusion-related reactions was 0.4%. Immunogenicity As with all therapeutic proteins, there is the potential for immunogenicity. In clinical trials, 33/443 (7.4%) of CYRAMZAtreated patients with post baseline serum samples tested positive for anti-ramucirumab antibodies using an enzyme-linked immunosorbent assay (ELISA). However, this assay has limitations in detecting anti-ramucirumab antibodies in the presence of ramucirumab; therefore, the incidence of antibody development may not have been reliably determined. Neutralizing antibodies were detected in 1 of the 33 patients who tested positive for anti-ramucirumab antibodies. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay 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 incidence of antibodies to CYRAMZA with the incidences of antibodies to other products may be misleading. DRUG INTERACTIONS No formal drug interaction studies have been conducted. TM

CYRAMZA (ramucirumab) injection

PA000IPAM00 – BS 9.25x13.25

CYRAMZATM (ramucirumab) injection

PA000IPAM00 – BS 9.25x13.25

Editorial Board EDITOR-IN-CHIEF

Patrick Medina, PharmD, BCOP Oklahoma University College of Pharmacy Tulsa, OK

Anjana Elefante, PharmD, BSc, BSc Pharm, RPh Roswell Park Cancer Institute Buffalo, NY

Dwight Kloth, PharmD, FCCP, BCOP

Timothy G. Tyler, PharmD, FCSHP

Fox Chase Cancer Center Philadelphia, PA

Desert Regional Medical Center Palm Springs, CA

Beth Faiman, PhD(c), MSN, APRN-BC, AOCN

Jim Koeller, MS

John M. Valgus, PharmD, BCOP

Christopher Fausel, PharmD

Christopher J. Lowe, PharmD

ASSOCIATE EDITOR-IN-CHIEF

Steve Stricker, PharmD, MS, BCOP Samford University McWhorter School of Pharmacy Birmingham, AL

John F. Aforismo, BSc Pharm, RPh, FASCP

University of Texas at Austin San Antonio, TX

Cleveland Clinic Taussig Cancer Institute Cleveland, OH

Indiana University Simon Cancer Center Indianapolis, IN

Indiana University Hospital Indianapolis, IN

David Baribeault, BS, BCOP

Rebecca S. Finley, PharmD, MS

Emily Mackler, PharmD, BCOP

Betty M. Chan, PharmD, BCOP

David C. Gammon, BSPh

Laura Boehnke Michaud, PharmD, BCOP, FASHP

RJ Health Systems International, LLC Wethersfield, CT

Boston, MA

USC/Norris Cancer Hospital Los Angeles, CA

Jefferson School of Pharmacy Philadelphia, PA

OncologyPharmacist.net Warwick, RI

University of Michigan Health System & College of Pharmacy Ann Arbor, MI

The University of Texas MD Anderson Cancer Center Houston, TX

University of North Carolina Hospitals and Clinics Chapel Hill, NC

Gary C. Yee, PharmD, FCCP, BCOP University of Nebraska College of Pharmacy Omaha, NE

Burt Zweigenhaft, BS

Onco360/OncoMed New York, NY

Marlo Blazer, PharmD, BCOP James Cancer Hospital & Solove Research Institute Columbus, OH

Heidi D. Gunderson, PharmD, BCOP Mayo Clinic Cancer Center Rochester, MN

Steven L. Dâ&#x20AC;&#x2122;Amato, RPh, BCOP Maine Center for Cancer Medicine Scarborough, ME

www.TheOncologyPharmacist.com

Lew Iacovelli, BS, PharmD, BCOP, CPP

Moses H. Cone Health System Greensboro, NC

LeAnn Best Norris, PharmD, BCPS, BCOP South Carolina College of Pharmacy Columbia, SC

Kamakshi V. Rao, PharmD, BCOP University of North Carolina Hospitals and Clinics Chapel Hill, NC

August 2014 I VOL 7, NO 3

From The EditorS PUBLISHING STAFF Senior Vice President, Sales & Marketing Nicholas Englezos nenglezos@the-lynx-group.com Senior Vice President, Sales & Marketing Philip Pawelko ppawelko@the-lynx-group.com Vice President/Director of Sales & Marketing Joe Chanley jchanley@the-lynx-group.com Group Director, Sales & Marketing John W. Hennessy jhennessy2@the-lynx-group.com Publishers Russell Hennessy rhennessy@the-lynx-group.com Cristopher Pires cpires@the-lynx-group.com Editorial Director Kristin Siyahian ksiyahian@the-lynx-group.com Managing Editor Kristen Olafson kolafson@the-lynx-group.com Copy Editors Sophie Chen Mollie Friedman Peggy Roeske Editorial Assistant Jennifer Brandt Production Manager Cara Nicolini

Patrick Medina, PharmD, BCOP Editor-in-Chief

Steve Stricker, PharmD, MS, BCOP Associate Editor-in-Chief

n this month’s issue of The Oncology Pharmacist (TOP), we present the fourth and final article in our series on oncology pharmacy safety. Christine Roussel, PharmD, BCOP, and Thomas H. Connor, PhD, discuss hazardous drug assessment, use of antineoplastic drugs in nononcology settings, oral chemotherapy, decontamination/cleaning, state legislative activities, and the new update to USP Chapter 800. One of the most interesting developments relates to actions taking place at the state level. The authors note, “The promulgation of new legislation related to safe handling of hazardous drugs by several states has forever changed the climate in which safe handling guidelines have been perceived.” Please participate in our reader poll (see below), which

ties into the issue of oncology pharmacy safety. We ask if you’ve collaborated with colleagues in developing safety protocols for the handling of potentially hazardous drugs. Roussel and Connor point out that “The growing use of hazardous drugs in nononcology practices and the increased utilization of oral hazardous drugs require the scope of safe handling practices to extend beyond traditional settings.” Please visit our website, www. TheOncologyPharmacist.com, and let us know if you have helped educate staff in other healthcare settings about potentially hazardous drugs. When you visit the TOP website to participate in the poll, please take the time to give us your feedback about what you see in print and online. We want to hear from you! l

Reader Poll

The Lynx Group President/CEO Brian Tyburski Chief Operating Officer Pam Rattananont Ferris Vice President of Finance Andrea Kelly Human Resources Jennine Leale Associate Director, Content Strategy & 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 Assistant Lora LaRocca Director, Digital Media Anthony Romano Web Content Managers David Maldonado Anthony Trevean Digital Programmer Michael Amundsen Meeting & Events Planner Linda Sangenito Senior Project Manager Jini Gopalaswamy Project Coordinators Mike Kodada Deanna Martinez IT Specialist Carlton Hurdle Executive Administrator Rachael Baranoski Administrative Coordinator Stephanie Ramadan Office Coordinator Robert Sorensen

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August 2014 I VOL 7, NO 3

Have you worked with colleagues outside of oncology to develop safe handling practices for hazardous drugs? o Yes o No

©iStockphoto.com/ Wavebreak

n their article addressing oncology pharmacy safety, Christine Roussel, PharmD, BCOP, and Thomas H. Connor, PhD, make it clear that “it’s not just oncology anymore”—hazardous drugs are found in many practice settings. Many healthcare professionals in nononcology settings may not be aware

of the potential hazards and/or may not be adequately trained. Roussel and Connor hope that oncology pharmacists can serve as conduits to help properly educate staff in all healthcare settings. Tell us if you’ve faced this situation. How does your institution address this issue?

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

The Oncology Pharmacist®, ISSN 1944-9607 (print); ISSN 1944-9593 (online) is published 4 times a year by Green Hill Healthcare Communications, LLC, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. Telephone: 732.656.7935. Fax: 732.656.7938. Copyright ©2014 by Green Hill Healthcare Communications, LLC. All rights reserved. The Oncology Pharmacist® logo is a registered trademark of Green Hill Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the Publisher. Printed in the United States of America. EDITORIAL CORRESPONDENCE should be addressed to EDITORIAL DIRECTOR, The Oncology Pharmacist®, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. E-mail: editorial@greenhillhc.com. YEARLY SUBSCRIPTION RATES: United States and possessions: individuals, $105.00; institutions, $135.00; single issues, $17.00. Orders will be billed at individual rate until proof of status is confirmed. Prices are subject to change without notice. Correspondence regarding permission to reprint all or part of any article published in this journal should be addressed to REPRINT PERMISSIONS DEPARTMENT, Green Hill Healthcare Communications, LLC, 1249 South River Road, Suite 202A, Cranbury, NJ 08512. The ideas and opinions expressed in The Oncology Pharmacist® do not necessarily reflect those of the Editorial Board, the Editorial Director, or the Publisher. Publication of an advertisement or other product mentioned in The Oncology Pharmacist® should not be construed as an endorsement of the product or the manufacturer’s claims. Readers are encouraged to contact the manufacturer with questions about the features or limitations of the products mentioned. Neither the Editorial Board nor the Publisher assumes any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this periodical. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosage, the method and duration of administration, or contraindications. 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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Conference News: AVBCC

Worksite Pharmacy Can Enhance Overall Drug Management of Patients With Cancer Wayne Kuznar

orksite pharmacies have unique advantages over local pharmacies in caring for employees with cancer. At the Fourth Annual Conference of the Association for Value-Based Cancer Care, Bill Raulerson, PharmD, director of On-Site Pharmacy Operations at Take Care Health Systems, Walgreens, described how their onsite pharmacies are meeting the needs of employees with cancer.1 At worksite healthcare pharmacies, the duties of pharmacists are expanded to include optimization of medication use, assistance with management of comorbidities, preventive care, and triaging when appropriate. In addition, pharmacists at onsite centers have better opportunities to develop

Bill Raulerson, PharmD

Florencio Calderon, PharmD, BCPS

relationships with employees. “We view the role of our pharmacists in the treatment of oncology patients as an oppor-

tunity to leverage that patient relationship,” Raulerson said. The advantages are patient access to a trusted clinician,

better communication, patient education, and patient advocacy. Low medication adherence rates, which are especially common with cancer patients, may be improved through the use of a worksite pharmacy. Raulerson said that healthcare expenses associated with nonadherence can cost up to $300 billion per year in the United States.2 Raulerson noted that “Patients filling prescriptions at worksite pharmacies are about 12% less likely to have a gap in therapy” compared with those who use a mail order pharmacy.3 Moreover, Raulerson said that onsite pharmacies have a 10% higher rate of adherence than local pharmacies. When a person with concomitant medical conditions such as diabetes, Continued on page 18

Conference News: ASCO Continued from cover

Exemestane Plus Ovarian Suppression a Valid Option in Premenopausal Early Breast Cancer The aromatase inhibitor exemestane was superior to tamoxifen when combined with ovarian function suppression (OFS) in preventing recurrence in premenopausal women with hormone-sensitive breast cancers. These were the findings of a joint analysis of 2 important phase 3 clinical trials, TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression on Ovarian Function Trial), that were presented at the American Society of Clinical Oncology 2014 annual meeting and pub- Olivia Pagani, MD lished simultaneously in the New England Journal of Photo by © ASCO/Silas Crews 2014. Medicine.1,2 Lead author, Olivia Pagani, MD, explained that yet been analyzed, so it is currently not possible to up until now exemestane has been used only in post- determine if tamoxifen alone is superior, equal, or menopausal women. “This analysis demonstrates inferior to hormonal therapy plus OFS. that an aromatase inhibitor is effective adjuvant The joint analysis of SOFT and TEXT included therapy for premenopausal women when combined 4690 patients from both trials enrolled in the OFSwith ovarian suppression. Exemestane [plus OFS] is containing arms. a valid alternative to tamoxifen [plus OFS] in young Chemotherapy was given at the discretion of the women with hormone-sensitive disease. It is a new treating physician, and 42.6% did not receive cheadjuvant treatment option that reduces recurrence motherapy. About 28% of the women who did not in this setting,” she stated. Pagani is clinical direc- get chemotherapy had tumors larger than 2 cm and tor of the Breast Unit at the Oncology Institute of some positive nodes. In a separate interview, Pagani Southern Switzerland in Bellinzona. said that the study suggests that exemestane plus OFS is used more frequently in Europe than in OFS could replace chemotherapy in some patients. the United States to achieve low estrogen levels “Our study suggests that for hormone-sensitive in patients with hormone-sensitive breast cancer. tumors, go for exemestane and OFS and you can Tamoxifen is considered the standard of care in this avoid chemotherapy,” Pagani stated. setting, and adjuvant chemotherapy is sometimes At a median follow-up of 68 months, 5-year used depending on the judgment of the oncologist disease-free survival was 91.1% with exemestane and patient preference. plus OFS versus 87.3% in the tamoxifen plus OFS Both SOFT and TEXT compared 5 years of group (P < .001). The 5-year rate of freedom from tamoxifen plus OFS versus 5 years of exemestane breast cancer was 92.8% in the exemestane-treated plus OFS. SOFT was a 3-arm trial comparing both patients compared with 88% in those who received of those treatment approaches versus tamoxifen tamoxifen (P < .001). Among patients who did alone; results of the tamoxifen-alone arm have not not receive chemotherapy and were treated with

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exemestane plus OFS, 97.6% of those in the TEXT population and 97.5% of those in the SOFT population were free of breast cancer at 5 years. The 5-year rate of freedom from recurrence at a distant site was 93.8% in the exemestane plus OFS group compared with 92% in the tamoxifen plus OFS group. At 5 years, overall survival was 95.9% in the exemestane group and 96.9% in the tamoxifen group. However, it is premature to determine survival, Pagani said. Side effects of both drugs were as expected. Adverse events that were more frequent with exemestane included fractures, musculoskeletal symptoms, vaginal dryness, decreased libido, and dyspareunia; those more frequently reported with tamoxifen included thromboembolic events, hot flushes, night sweats, and urinary incontinence. Gynecologic cancers were reported in 7 exemestane-treated patients and in 9 patients in the tamoxifen group; endometrial cancers occurred in 2 and 5 patients, respectively. About 30% of patients in both arms experienced grade 3 or 4 adverse events. Experts said that they were awaiting results of the tamoxifen-alone arm of the TEXT trial to see whether these findings would be practice changing. l References

1. Pagani O, Regan MM, Walley B, et al. Randomized comparison of adjuvant aromatase inhibitor (AI) with exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): joint analysis of IBCSG TEXT and SOFT trials. Presented at: 50th Annual Meeting of the American Society of Clinical Oncology; May 30-June 3, 2014; Chicago, IL. Abstract LBA1. 2. Pagani O, Regan MM, Walley BA, et al; the TEXT and SOFT Investigators and the International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014;371(2):107-118.

Continued on page 13

August 2014 I VOL 7, NO 3

Oncology Pharmacy Safety

Chemotherapy: Current and Emerging Issues… providers will need to be aware of, including hazardous drug assessment, use of antineoplastic drugs in nononcology settings, oral chemotherapy, decontamination/cleaning, state legislative activities, and US Pharmacopeial Convention (USP) Chapter 800.4 The clinical utility of hazardous drugs is expanding rapidly, and new challenges are arising for their safe use and handling. Occupational safety and health organizations and healthcare professionals are working hard to create safety guidance documents that keep pace with the changing environment. The growing use of hazardous drugs in nononcology practices and the increased utilization of oral hazardous drugs require the scope of safe handling practices to extend beyond traditional settings. The promulgation of new legislation related to safe handling of hazardous drugs by several states has forever changed the climate in which safe handling guidelines have been perceived. With the revamped USP Chapter 800 for hazardous drug compounding, oncology pharmacists’ and nurses’ unique skill sets should be shared beyond their disciplines. Historically, safe handling guidance documents have been recommendations that are only followed on a voluntary basis. Occupational Safety and Health Administration (OSHA) inspections are infrequent and generally conducted only in response to reports of violations. However, states like Washington,5 California,6 and North Carolina7 are leading the charge in establishing state laws for the safe handling of hazardous drugs with consequences for when they are not followed. With guidance from OSHA,8 the National Institute for Occupational Safety and Health (NIOSH),9 the American Society of Health-System Pharmacists,10 the Oncology Nursing Society,11 and USP,12 it is important for senior management in hospitals and priTable 1

vate oncology practices, and for owners and managers of retail pharmacies, to perceive this information as mandatory requirements to ensure employee protection. While implementation of medical surveillance may meet with greater resistance, proper policies for the identification and labeling of hazardous drugs, as well as adequate facilities, equipment, and personal protective equipment (PPE), should be clear in standard operating

aging (documented to be as high as 100% contaminated when leaving the manufacturer) and through indirect contact by touching surfaces that have been contaminated.14 Additional routes of exposure include inhalation (breathing contaminated aerosols and vapors), ingestion via hand-to-mouth contact (eating, drinking, gum chewing) in areas where hazardous drugs are stored or compounded, and injection (finger sticks, vial breakage).15

The promulgation of new legislation related to safe handling of hazardous drugs by several states has forever changed the climate in which safe handling guidelines have been perceived. procedures. The hope is that this article challenges the oncology community to reach out to other practice sites where hazardous drugs are handled and share the safety practices that have evolved over the past few decades. The Risk of Hazardous Drugs The healthcare setting has the largest and most diverse mix of chemicals that are hazardous to humans—more than any other occupational setting—ranging from drugs with acute effects to those linked to reproductive toxicity and cancer.13 Surface contamination with hazardous drugs in pharmacies and nursing administration areas has been extensively documented.2 Considering that the existing literature has only evaluated the presence of less than 5% of the known hazardous drugs found in the healthcare workplace, the incidence and magnitude of surface contamination are likely higher. The main vector of exposure is dermal contact directly with drugs and drug pack-

Of greater concern than the presence of hazardous drugs in the work environment is documentation that the drugs and their metabolites have been found in the urine of exposed healthcare workers.3 Similarly, studies of worker exposure have only been conducted on a small percentage of hazardous drugs, and positive urine samples have been detected in pharmacists, pharmacy technicians, and nurses, including those not directly involved in compounding.3 Some investigations into biomarkers of effect have shown associations between surface contamination and the presence of drugs in the urine,16-18 while others have demonstrated significant associations between exposure and biomarkers of genotoxicity in exposed healthcare workers.3 Hazardous Drug Identification and Hazard Assessment The first step in any safe handling program is the identification and risk assessment of hazardous drugs in any given workplace.

H azardous Drugs in Many Practice Settings: “It’s Not Just Oncology Anymore”

Specialty

Drug

Rheumatology

Cyclophosphamide, azathioprine, rituximab, abatacept, tacrolimus, methotrexate

Transplant

Cyclosporine, tacrolimus, sirolimus, mycophenolate

Infectious diseases

Ganciclovir

Obstetrics/gynecology

Methotrexate

Urology

Mitomycin, bacillus Calmette-Guérin (BCG), valrubicin

Surgery

Mitomycin: ocular, bladder, tracheal stricture

Emergency department

Methotrexate

Ophthalmology

Mitomycin

Community pharmacy

All of the above in solid dosage forms

August 2014 I VOL 7, NO 3

Continued from cover

It is recommended to start the process by examining NIOSH’s Hazardous Drug List, but institutions can and should create their own facility-specific list based on their current drug usage. The NIOSH list was last updated in June 2012,13 and the proposed changes for the 2014 update include the addition of several oral agents (eg, erlotinib, fluconazole, spironolactone, topiramate, warfarin).19 Institutions in which hazardous drugs are present should have a mechanism for updating their list as new drugs come into the facility. There are many variations for further categorizing hazardous drugs, with some institutions separating antineoplastic drugs from hazardous drugs with precautions similar to those for the antineoplastic drugs and grouping together teratogens, reproductive toxins, and hormones.20-22 Some facilities further separate risk levels by formulation, using different precautions and PPE when handling hazardous intravenous drugs compared with hazardous oral drugs, and even determining which drugs should be counted or manipulated within a biological safety cabinet (BSC) versus oral drugs that have been classified as safe to be handled in the general environment as long as the dosage form is not altered. Both USP Chapter 8004 and OSHA’s Technical Manual8 acknowledge that dispensing nonantineoplastic hazardous drugs in unit-dose and unit-of-use dosage forms that are not altered (cut, crushed, etc) likely does not impart significant risk to the employee. To better address these and other issues, NIOSH has proposed listing hazardous drugs in 3 categories: (1) antineoplastic drugs (based on American Hospital Formulary Service classification 10:00), (2) nonantineoplastic drugs, and (3) drugs primarily with reproductive risks. Along with these changes, NIOSH will also provide additional guidance on engineering controls and PPE.19 In hospitals and cancer centers, pharmacists can provide knowledge about pharmacology, dosage formulation, and compounding, while nurses can address administration concerns and patient-specific issues that have required process and administration changes at the bedside. A team approach can enhance the ability to evaluate all aspects of a drug and its potential risks, from receiving to preparation, administration, disposal, and patient excretion. The risk stratification approach to hazardous drug handling may increase compliance by targeting the medications and situations most likely to cause the greatest exposure and risk to the employee. Use of Antineoplastic Drugs in Nononcology Settings Cancer patients are not the only patients being treated with antineoplastic

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Oncology Pharmacy Safety drugs.23,24 Many drugs that have typically been considered just for the treatment of cancer are now being used in other specialties (Table 1). As Polovich and Giesker noted in 2011, “Oncology units where patients with cancer receive chemotherapy are not the only settings where hazardous drugs are found. Because of the increased use of antineoplastic agents for nononcology indications, nurses’ risk for occupational exposure is distributed more widely than in the past.”23 Often, healthcare professionals who are administering antineoplastic drugs in other settings may not be aware of their potential occupational hazards and/or may not be adequately trained in their use and disposal. General inpatient units in hospitals, as well as procedural areas such as the surgery department and interventional radiology, may manage hazardous drugs as only a small percentage of total patient care activities; thus, these handling activities may be associated with less robust procedures and staff education as well as decreased access to appropriate equipment or supplies for safe handling and disposal. Oncology pharmacists and nurses have valuable insight and can help inpatient and procedural areas perform a gap analysis, develop standardized processes, and share knowledge gained from experience. Sharing up-to-date regulatory documents and employing face-to-face collaborative approaches to reviewing existing policies related to the safe handling and administration of hazardous drugs are hugely beneficial for institutions as a whole. With the increased prescribing of hazardous drugs for nononcology conditions, retail pharmacies often carry many solid dosage forms of NIOSH-listed drugs, some of which are uncoated pressed-powder tablets that easily liberate hazardous drug powder onto the work surface or into the air. Retail pharmacies often purchase large stock bottles of medications, and the dust liberated in production and transportation accumulates in the bottom of the bottles. Inverting a stock bottle of uncoated tablets to get them out often leads to spilling powder and sending it into the air. The range of hazardous drugs in retail chains is increasing as a result of expanding their scope of services in an effort to increase revenue and remain competitive, including special ordering medications to help loyal customers. While few retail pharmacies may believe they carry many hazardous drugs, about 10% of the top 100 drugs in the United States either by sales or number of units dispensed from 2013 to 2014 are listed as hazardous by NIOSH.13,14,25 Prefilled syringes of hormonal-modulating and immunotherapy agents as well as injectable vials of methotrexate can be found on the shelves of retail pharmacies. In the busy retail pharmacy environment,

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Christine Roussel, PharmD, BCOP

Table 2

age the dosage form and introduce powdered contaminants into the work area. “Counting coated tablets and capsules does not require a C-PEC [containment primary engineering control], as long as they are not altered or broken.”4 The oral route of administration for hazardous drugs has become increasingly more common, with 25% of the oncology drug pipeline intended for oral self-administration.27 Retail pharmacies, specialty pharmacies, and physician practices with in-house dispensaries must think about safe handling from a different perspective. Recently, several documents have been published with a focus on oral chemo-

Thomas H. Connor, PhD

Summary of State Bills on Hazardous Drugs

State/Bill

Year

Comments

Washington—Senate Bill 5594

2011

Does not include medical surveillance

California—Assembly Bill 1202

2013

Applies only to antineoplastic drugs

North Carolina—House Bill 664

2013

Currently in Senate

Maryland—Regulations proposed by Maryland Occupational Safety and Health

2013

Currently in committee

staffs traditionally wear minimal to no PPE, and the positions of retail pharmacy technicians are predominantly staffed by a younger workforce with a relatively high turnover rate. This reinforces the fact that it is crucial for all healthcare settings and pharmacies to identify and label hazardous drugs and to properly educate staff. Oral Chemotherapy/Nonliquid Hazardous Drugs The guidelines from several organizations8-12 state that hazardous drugs in solid dosage forms pose a health risk to employees. The level of risk varies depending on the formulation. The highest-risk formulation is uncoated pressed-powder tablets that liberate dust particles, causing surface contamination and creating airborne drug dust that can be directly inhaled by employees and can contaminate the work area.8 Capsules and coated tablets are unlikely to produce dust unless broken in handling or if they are crushed or cut, which can pose a risk for surface contamination. OSHA’s Technical Manual states: The handling of nonliquid forms of HD’s [hazardous drugs] requires special precautions as well. Tablets which may produce dust or potential exposure to the handler should be counted in a BSC. Capsules, i.e., gel-caps or coated tablets, are unlikely to produce dust unless broken in handling. These are counted in a BSC on equipment designated for HD’s only, because even manual counting devices may be covered with dust from the drugs handled. Automated counting machines should

not be used unless an enclosed process isolates the hazard from the employee(s).8 While many retail pharmacies have separate counting trays for penicillin and other β-lactam drugs, many pharmacies do not have separate counting trays for hazardous oral drugs, let alone have negative pressure rooms with externally vented BSCs. Common examples of hazardous drugs dispensed in most pharmacies in uncoated pressed β-powder formulation include generic cyclophosphamide, methotrexate, melphalan, 6-mercaptopurine, and others.26 When finalized, USP Chapter 800 will provide additional information detailing the dispensing of hazardous drug dosage forms not requiring alteration: HDs in unit-dose or unit-of-dose packaging that do not require any further alteration before delivery to the patient or the patient’s caregiver may be dispensed without any further requirements for containment unless required by the manufacturer. If the entity’s SOPs [standard operating procedures] permit, non-antineoplastic HDs that require only transfer from the manufacturer’s package to a prescription container may be dispensed without any further requirements for containment unless required by the manufacturer. Counting of HDs should be done carefully, and clean equipment should be dedicated for use with these drugs.4 The finalized USP Chapter 800 will state that tablet and capsule forms of HDs shall not be placed in automated counting machines, as mechanical stress may dam-

therapy.28-34 While standards of practice dictate that nurses administering intravenous chemotherapy should have specific qualifications (such as additional training, passing facility-specific competencies, and preferably the Oncology Nursing Society Chemotherapy Biotherapy Certificate), currently no additional requirements are recommended for nurses administering oral hazardous drugs.27 Patients and caregivers must also be educated about the safe handling of hazardous drugs while self-administering in the home, such as wearing gloves during administration of drugs, handling patient waste and changing diapers, proper storage of drugs, and disposal of waste materials. Parents who may be administering liquid formulations of hazardous drugs to their children (potentially for years) must be educated about how to protect themselves and other members of the household. In addition to safety recommendations for oral chemotherapy, both for patient education and healthcare practitioners, Goodin and colleagues30 made recommendations to drug manufacturers. To reduce the possibility of exposure for healthcare personnel and family members or other caregivers, the authors recommended either dispensing oral hazardous drugs in more appropriately sized packages to better approximate treatment cycles or considering unit-dose packaging with the goal of minimizing product manipulation during dispensing. Special consideration should also be paid to mail order pharmacies and other Continued on page 10

August 2014 I VOL 7, NO 3

Oncology Pharmacy Safety

Chemotherapy: Current and Emerging Issues… facilities that use automated dispensing machines for both nonhazardous and hazardous drugs in pill form, as these tend to produce dust, which can be inhaled by workers and contaminate surfaces, which can lead to dermal uptake.35-37 Decontamination and Cleaning of Surfaces Contaminated With Hazardous Drug Residues USP Chapter 79712 defines decontamination as “inactivation, neutralization, or removal of hazardous drugs, usually by chemical means,” whereas deactivation is the “treatment of a hazardous drug

Table 3

Safe decontamination product contains bleach as the first step and sodium thiosulfate as a neutralizer for the second step; HDClean is a proprietary blend of quaternary ammonium compounds. It should be noted that using isopropyl alcohol to disinfect a BSC will not decontaminate any hazardous drugs, but rather could put the drug into solution, and the wiping process may result in the spread of contamination.10 Decontamination procedures are vital safety measures in any facility that handles hazardous drugs. While the process and frequency were previously not well

ashington State’s Hazardous Drugs Control Program W Mandatory Elements

A written inventory of hazardous drugs in the workplace A current hazard assessment for the hazardous drugs Hazardous drugs policies and procedures that cover, but are not limited to: Engineering controls (equipment use and maintenance) Personal protective equipment Safe handling practices (receiving and storage, labeling, preparing, administering, and disposing of hazardous drugs) Cleaning, housekeeping, and waste handling Spill control Personnel issues (eg, exposure of pregnant workers) Training with another chemical, heat, ultraviolet lights, or other agent to create a less hazardous agent.” Cleaning is described as “the removal of soil (e.g., organic and inorganic material) from objects and surfaces normally accomplished manually or mechanically using water with detergents or enzymatic products.” Often these terms are used interchangeably and incorrectly. Given the large number of hazardous drugs in use and the wide variation in their chemical nature and makeup, no single agent will successfully decontaminate or clean surfaces after exposure to most of these drugs.38-45 Sodium hypochlorite (bleach) is probably used most often for decontamination. Bleach is a strong oxidizer shown to deactivate some hazardous drugs. The availability of commercial products such as Surface Safe (Hospira Healthcare Corporation, SaintLaurent, Quebec, Canada; http://www. hospira.ca/english/surfacesafe.aspx) and HDClean (ChemoGLO, LLC, Chapel Hill, North Carolina; http://www.che moglo.com/WhatIsHDClean.aspx) has increased convenience, but they have only been validated with a small number of drugs and may be cost prohibitive in some facilities. The 2-part Surface

August 2014 I VOL 7, NO 3

defined in US documents,8,9 USP Chapter 800 provides more detailed guidance, and it is expected that more information will be released within the next few years as the data documenting surface contamination continue to accumulate. Important considerations for decontamination of BSCs include donning full PPE and ensuring proper ventilation. While it is ideal for the sash of the BSC to remain down during decontamination, often it is necessary to lift the sash of the BSC; thus, employees must wear a respirator such as an N-95 (not a surgical mask). USP Chapter 800 mentions the importance of performing cleaning in areas that are sufficiently ventilated, but does not provide further detail. Because there is a risk of hazardous vapors generated by liberating hazardous drugs or from cleaning agents, the exhaust fan and blower of the BSC must always remain on during the decontamination process to maintain exhaust.8 A BSC should be decontaminated at least weekly, as well as prior to environmental maintenance and certification, after a chemotherapy spill or if contamination is suspected, and after any interruption in ventilation occurs. Cleaning with water and an alkaline

Continued from page 9

detergent, followed by thorough rinsing, is also an acceptable method when the physical situation permits, as hazardous residue would be liberated and then rinsed away.8 All waste material generated during decontamination is considered hazardous and should be discarded in appropriate waste containers. Using spray bottles inside BSCs should be avoided, owing to effects on HEPA filters and the production of aerosols. The final step before compounding is to wipe down the BSC with alcohol to reestablish sterility. Cleaning and disinfection of the hood should be conducted per USP 797.12 Surface decontamination is also appropriate for pharmacy counters with hazardous drug traffic as well as nursing areas where chemotherapy is administered. State Legislative Activities Related to Hazardous Drugs In response to the growing concern about healthcare workers being exposed to hazardous drugs during the course of their working life and the wealth of new information being published internationally in the literature, several states have enacted, or are in the process of enacting, legislation aimed at protecting workers from the adverse effects of antineoplastic and other hazardous drugs. Most legislation is based on the guidelines published by NIOSH in 2004.9 Table 2 summarizes the current activities at the state level.

Washington State In 2011, the Washington State legislature passed a bill requiring the Department of Labor & Industries to adopt rules for the safe handling of hazardous drugs.5 The legislation stated the following: Pursuant to RCW 49.17.465, the department is required to ‘adopt by rule requirements for the handling of antineoplastic and other hazardous drugs in health care facilities regardless of the setting.’ The statute requires the department’s rules ‘be consistent with and not exceed provisions adopted by the National Institute for Occupational Safety and Health’s (NIOSH) 2004 alert on preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings as updated in 2010.’…The legislature also directed the department to consider input from hospitals, organizations representing health care personnel, other stakeholders in adopting the rules.46 Adopted on January 3, 2012, the hazardous drugs rule requires employers to develop and implement a written hazardous drugs control program to protect workers if there is a reasonably anticipated occupational exposure to one or more hazardous drugs. Washington State adopted the NIOSH definition of hazardous drugs and the NIOSH Hazardous Drug List for its documents. The program is being implemented in stages, and as of the start of 2015, employers

must have completed and implemented a written hazardous drugs control program. Employee training must be implemented by July 2015, and, finally, appropriate ventilated cabinets must be installed by January 2016. All healthcare facilities where employees face occupational exposure must comply, including hospitals, clinics, nursing homes, laboratories, offices, veterinary medicine clinics, retail pharmacies, home healthcare agencies, and research laboratories where a healthcare provider offers healthcare to patients. The rule allows for alternative precautions when the hazard assessment determines a low occupational exposure risk while preparing hazardous drugs other than chemotherapy agents, for example, from crushing and splitting tablets or drawing drug into a syringe. These alternatives could include temporarily designating a space as the preparation area, using appropriate PPE, and instituting specific cleaning procedures. The Washington State Division of Occupational Safety & Health has created a Hazardous Drugs Advisory Committee to aid employers in implementation of the requirements by discussing new NIOSH recommendations, scientific and technological developments, and other issues related to implementing this rule, via live meetings, a hazardous drugs webpage for resources, and a hazardous drugs email listserv.47 Washington State’s hazardous drugs rule does not include medical surveillance in the final document, as the topic was removed from the proposed rule because of concerns that NIOSH was updating its statements on the topic during the drafting process. Washington State’s written hazardous drugs control program specifies a list of elements that must be addressed and must include worker input during the creation process (Table 3). Healthcare and other workers potentially impacted by the Washington State rule include all those who work in areas where hazardous drugs are handled (Table 4). California The Cal/OSHA Occupational Exposure to Antineoplastic Drugs Advisory Meeting in June 2014 discussed implementation of Assembly Bill (AB) 1202 and Labor Section 144.8 regarding occupational safety and health standards: hazardous drugs. The California bill refers only to antineoplastic drugs and not all hazardous drugs.6,48 The language noted: It is the intent of the Legislature to require the Occupational Safety and Health Standards Board to adopt standards consistent with the NIOSH alert regardless of setting in order to protect health care personnel from hazardous exposure to these drugs. The board shall adopt an occupational

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Oncology Pharmacy Safety safety and health standard for the handling of antineoplastic drugs in health care facilities regardless of the setting. In developing the standard, the board shall consider input from hospitals, practicing physicians from impacted specialties, including oncology, organizations representing health care personnel, including registered nurses and pharmacists, and other stakeholders, and shall determine a reasonable time for facilities to implement new requirements imposed by the adopted standard. The standard, to the extent feasible, shall be consistent with and not exceed recommendations in the NIOSH 2004 alert entitled ‘Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings,’ as updated in 2010. The standard may incorporate applicable updates and changes to NIOSH guidelines. North Carolina The state of North Carolina is currently debating the bill in the Senate, after being passed by the House in 2013.7 Whereas, in this alert, the NIOSH presents a standard precautions or universal precautions approach to handling hazardous drugs safely, meaning that it recommends that all hazardous drugs be handled as outlined in the alert; Now, therefore, The General Assembly of North Carolina enacts: The General Assembly finds that health care personnel who work with or near hazardous drugs in health care settings may be exposed to these agents in the air, on work surfaces, clothing, and medical equipment or through patient contact. It is the intent of the General Assembly to require health care facilities to follow rules requiring compliance with all aspects of alerts from the National Institute for Occupational Safety and Health regardless of the setting in order to protect health care personnel in this State from hazardous exposure to such drugs. USP Chapter 800 An important new development related to the safe handling of hazardous drugs is the new USP chapter, Hazardous Drugs—Handling in Healthcare Settings, which was recently available for public comment. Chapter 8004 will supersede the hazardous drug section in USP Chapter 7979 (http://www.usp.org/usp-nf/ notices/compounding-notice). Because Chapter 800 will be enforced by some state boards of pharmacy, it will have an impact on the preparation/compounding of hazardous drugs. Summary With new challenges to both employees and employers to ensure a safe working environment when antineoplastic and other hazardous drugs are present, it will be imperative that all parties are aware of new recommendations and regulations that will affect their work practices. Washington State and California already

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have legislation focused on the safe handling of hazardous drugs, and other states are following close behind with their own legislation or regulations. As NIOSH, USP, and other organizations move forward on activities aimed at protecting workers from hazardous drugs, healthcare workers everywhere will benefit from safer working conditions in their endeavors to treat seriously ill patients with an everexpanding armament of drugs. l References

1. Roussel C, Connor TH. Chemotherapy and pharmacy: a toxic mix? Oncol Pharmacist. 2013;6(2):1, 32-33. 2. Roussel C, Connor TH. Chemotherapy: every step you take, every move you make…. Oncol Pharmacist. 2013;6(4):1, 8-12. 3. Roussel C, Connor TH. Chemotherapy: biomarkers of exposure, effect, reproductive hazards, and cancer. Oncol Pharmacist. 2014;7(1):1, 10-13, 18. 4. US Pharmacopeial Convention. General Chapter <800> Hazardous Drugs—Handling in Healthcare Settings. http://www.usp.org/usp-nf/notices/compound ing-notice. Accessed June 20, 2014. 5. Washington State Senate Bill 5594. 62nd Leg, 2011 Regular Session. http://apps.leg.wa.gov/documents/ billdocs/2011-12/Pdf/Bills/Senate%20Bills/5594.pdf. Accessed June 20, 2014. 6. California Assembly Bill 1202. 2013-2014 Regular Session. http://openstates.org/ca/bills/20132014/AB1 202/. Accessed June 20, 2014. 7. North Carolina House Bill 644. 2013-2014 Regular Session. http://www.ncleg.net/gascripts/BillLookUp/ BillLookUp.pl?Session=2013&BillID=h644. Accessed June 20, 2014. 8. Occupational Safety and Health Administration. Controlling occupational exposure to hazardous drugs. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2. html. Published January 20, 1999. Accessed June 20, 2014. 9. Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. Preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings. www.cdc.gov/niosh/ docs/2004-165/. Published September 2004. Accessed June 20, 2014. 10. American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health Syst Pharm. 2006;63:1172-1193. 11. Polovich M, Bolton DL, Eisenberg S, et al, eds. Safe Handling of Hazardous Drugs. 2nd ed. Pittsburgh, PA: Oncology Nursing Society; 2011. 12. US Pharmacopeial Convention. Revised Chapter <797> Pharmaceutical Compounding—Sterile Preparations. http://www.pbm.va.gov/linksotherresourc es/docs/USP797PharmaceuticalCompoundingSterile Compounding.pdf. Accessed July 15, 2014. 13. Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012. DHHS (NIOSH) Publication No. 2012-150. http://www.cdc.gov/niosh/ docs/2012-150/. Published June 2012. Accessed June 20, 2014. 14. Connor TH, Sessink PJ, Harrison BR, et al. Surface contamination of chemotherapy drug vials and evaluation of new vial-cleaning techniques: results of three studies. Am J Health Syst Pharm. 2005;62:475-484. 15. Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. Personal Protective Equipment for Health Care Workers Who Work With Hazardous Drugs. DHHS (NIOSH) Publication No. 2009-106. http://www.cdc.gov/niosh/docs/wp-solu tions/2009-106/pdfs/2009-106.pdf. Published October 2008. Accessed June 20, 2014. 16. Pethran A, Schierl R, Hauff K, et al. Uptake of antineoplastic agents in pharmacy and hospital personnel. Part I: monitoring of urinary concentrations. Int Arch Occup Environ Health. 2003;76(1):5-10. 17. Connor TH, DeBord G, Pretty JR, et al. Evaluation of antineoplastic drug exposure of health care workers at three university-based US cancer centers. J Occup Environ Med. 2010;52:1019-1027. 18. Villarini M, Dominici L, Piccinini R, et al. Assessment of primary, oxidative and excision repaired DNA damage in hospital personnel handling antineoplastic drugs. Mutagenesis. 2011;26(3):359-369. 19. Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2014. DHHS (NIOSH) Publication No. 2014-xxx [In preparation]. http://www.cdc.gov/ niosh/topics/hazdrug/. Accessed July 15, 2014. 20. Chaffee BW, Armistead JA, Benjamin BE, et al. Guidelines for the safe handling of hazardous drugs: consensus recommendations. Am J Health Syst Pharm. 2010;67(18):1545-1546.

Table 4 Potentially Affected Workers Identified by Washington State

Pharmacists and pharmacy technicians Physicians and physician assistants Nurses and nursing assistants Patient care assistants, such as healthcare assistants or nursing assistants Surgical personnel Home healthcare workers Veterinarians and veterinary technicians Environmental services employees in healthcare facilities (including workers involved with housekeeping, laundry, or waste disposal) Employees in healthcare facilities who ship or receive hazardous drugs from the manufacturer or distributor 21. Badry N, Fabbro J, de Lemos ML. Hazards in determining whether a drug is hazardous. J Oncol Pharm Pract. 2013;20(4):312-315. 22. Kaestli L-Z, Fonzo-Christe C, Bonfillon C, et al. Development of a standardised method to recommend protective measures to handle hazardous drugs in hospitals. Eur J Hosp Pharm. 2013;20(2):100-105. 23. Polovich M, Giesker KE. Occupational hazardous drug exposure among non-oncology nurses. Medsurg Nurs. 2011;20(2):79-85, 97. 24. Menonna-Quinn D. Safe handling of chemotherapeutic agents in the treatment of nonmalignant diseases. J Infus Nurs. 2013;36(3):198-204. 25. Drugs.com. U.S. pharmaceutical sales - Q4 2013. http://www.drugs.com/stats/top100/sales. Updated February 2014. Accessed July 15, 2014. 26. Drug Information Handbook. 23rd ed. Hudson, OH: Lexi-Comp, Inc; 2014. 27. Neuss MN, Polovich M, McNiff K, et al. 2013 updated American Society of Clinical Oncology/ Oncology Nursing Society chemotherapy safety standards including standards for the safe administration and management of oral chemotherapy. J Oncol Pract. 2013;9(suppl 2):S5-S13. 28. Griffin E. Safety considerations and safe handling of oral chemotherapy agents. Clin J Oncol Nurs. 2003;7(suppl 6):25-29. 29. Simmons CC. Oral chemotherapeutic drugs: handle with care. Nursing. 2010;40(7):44-47. 30. Goodin S, Griffith N, Chen B, et al. Safe handling of oral chemotherapeutic agents in clinical practice: recommendations from an international pharmacy panel. J Oncol Pract. 2011;7(1):7-12. 31. Meier K, Griffith N, Chen B, et al. Safe handling of oral chemotherapeutic agents: a European perspective. Eur J Oncol Pharm. 2011;5(2):4-10. 32. McLauchlan R. Safe dispensing of oral chemotherapy. Safety Considerations Oncol Pharm. Fall 2011 (special ed). 33. Wakui N, Ookubo T, Iwasaki Y, et al. Development of a closed drug preparation method for oral anticancer drugs. J Oncol Pharm Pract. 2013;19(4):315-320. 34. Si P, Chan A. Common toxicities of oral anticancer agents: an overview. Safety Considerations Oncol Pharm. Fall 2011 (special ed). 35. Fent KW, Durgam S, Aristeguieta C, et al; Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. Health Hazard Evaluation Report: Exposures to Pharmaceutical Dust at a Mail Order Pharmacy—Illinois. http://www.cdc.gov/ niosh/hhe/reports/pdfs/2010-0026-3150.pdf. NIOSH HETA no. 2010-0026-3150. Published December 2011. Accessed June 20, 2014. 36. Fent KW, Tapp L, Wiegand D; Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. Health Hazard Evaluation Program: Evaluation of Safety Climate, Health Concerns, and Pharmaceutical Dust Exposures at a Mail Order Pharmacy. Report no. 2012-0044-3199. http:// www.cdc.gov/niosh/hhe/reports/pdfs/2012-0044-3199. pdf. Published December 2013. Accessed June 20, 2014. 37. Fent KW, Durgam S, Methner M; Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. Health Hazard Evaluation Program: Evaluation of Pharmaceutical Dust Exposures at an Outpatient Pharmacy. Report no. 20100078-3177. http://www.cdc.gov/niosh/hhe/reports/ pdfs/2010-0078-3177.pdf. Published April 2013.

Accessed June 20, 2014. 38. Chu WC, Hon CY, Danyluk Q, et al. Pilot assessment of the antineoplastic drug contamination levels in British Columbia hospitals pre- and post-cleaning. J Oncol Pharm Pract. 2012;18(1):46-51. 39. Hon CY, Chua PP, Danyluk Q, et al. Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: a pilot study. J Oncol Pharm Pract. 2014;20(3):210-216. 40. Queruau Lamerie T, Nussbaumer S, Décaudin B, et al. Evaluation of decontamination efficiency of cleaning solutions on stainless steel and glass surfaces contaminated by 10 antineoplastic agents. Ann Occup Hyg. 2013;57(4):456-469. 41. Lé LM, Jolivot PA, Sadou Yaye H, et al. Effectiveness of cleaning of workplace cytotoxic surface. Int Arch Occup Environ Health. 2013;86(3):333-341. 42. Lee S-G, Ambados F, Tkaczuk M, et al. Paclitaxel exposure and its effective decontamination. J Pharm Pract Res. 2009;39(3):181-185. 43. Roberts S, Khammo N, McDonnell G, et al. Studies on the decontamination of surfaces exposed to cytotoxic drugs in chemotherapy workstations. J Oncol Pharm Pract. 2006;12(2):95-104. 44. Touzin K, Bussières JF, Langlois E, et al. Pilot study comparing the efficacy of two cleaning techniques in reducing environmental contamination with cyclophosphamide. Ann Occup Hyg. 2010;54(3):351-359. 45. BC Cancer Agency. BC cancer agency pharmacy practice standards for hazardous drugs. Module 1: safe handling of hazardous drugs. http://www.bccancer. bc.ca/NR/rdonlyres/2F1E0F82-D308-4E94-ABC0-1BF 1CCCE2FC3/59972/2Module1.pdf. Published January 2012. Updated April 3, 2014. Accessed June 20, 2014. 46. Washington State Dept of Labor & Industries. Concise explanatory statement: hazard drugs. Adopted January 2012; effective January 2014. http://www.lni. wa.gov/rules/AO11/10/1110CES.pdf. Accessed June 20, 2014. 47. Washington State Dept of Labor & Industries. Questions & answers about the new hazardous drugs rule. http://www.lni.wa.gov/Safety/Topics/AtoZ/Hazard ousDrugs/qna.asp. Accessed June 20, 2014. 48. State of California Dept of Industrial Relations. Ca.gov website. Cal/OSHA: Occupational exposure to neoplastic drugs advisory meeting. http://www.dir. ca.gov/dosh/doshreg/Antineoplastic-Drugs/. Accessed June 20, 2014.

Disclaimers The findings and conclusions of this presentation have not been formally disseminated by NIOSH and should not be construed to represent any agency determination or policy. Mention of company names or products does not constitute endorsement by the National Institute for Occupational Safety and Health.

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Take a bite out of G-CSF acquisition costs* GRANIX is another option in short-acting G-CSF therapy TM

GRANIX™ is an option for hospitals and payers to consider when determining health system budgets » FDA approved through the rigorous BLA† process » Teva’s short-acting G-CSF was first introduced in Europe in 2008 and is available in 42 countries‡1 » GRANIX J Code: J 1446-Injection, tbo-filgrastim, 5 micrograms, effective January 1, 2014 †Biologics License Application. ‡As of February 2014. *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.

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 colonystimulating 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. » 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. Data on file. Teva Pharmaceuticals: Filgrastim MA Approvals Worldwide. February 2014.

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©2014 Cephalon, Inc., a wholly-owned subsidiary of Teva Pharmaceutical Industries Ltd. GRANIX is a trademark of Teva Pharmaceutical Industries Ltd. GRX-40178 February 2014. VOLAll 7,rights NO reserved. 3

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Loratadine and Bone Pain Pegfilgrastim, which mobilizes white blood cells that fight infection, is indicated by the US Food and Drug Administration for the treatment of cancer patients with nonmyeloid malignancies who are receiving anticancer drugs that are associated with clinically significant febrile neutropenia.1 Although pegfilgrastim is a highly effective drug, about half of the

patients who receive it experience moderate to severe bone pain that can interfere with quality of life and compromise adherence to treatment.2 “The mechanism of this bone pain is unclear,” said Joanna Schwartz, PharmD, BCOP, of Albany College of Pharmacy and Health Sciences in Colchester, Vermont, one of the authors of a phase 2 pilot study of

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 non-myeloid 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 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)] • Potential for Tumor Growth Stimulatory Effects on Malignant Cells [see Warnings and Precautions (5.5)] 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.

loratadine for the prevention of pegfilgrastim-induced bone pain (PIP). Lead author was Julia Moukharskaya, MD, of the University of Vermont College of Medicine in Burlington. Schwartz noted that granulocyte colony-stimulating factor (G-CSF)– induced bone marrow expansion of white blood cell precursors has been associated with histamine release and

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-US-approved 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. 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 There are no adequate and well-controlled studies of GRANIX in pregnant women. In an embryofetal developmental study, treatment of pregnant rabbits with tbo-filgrastim resulted in adverse embryofetal findings, including increased spontaneous abortion and fetal malformations at a maternally toxic dose. GRANIX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In the 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 (AUC0-24) 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. ©2013 Cephalon, Inc., a wholly owned subsidiary of Teva Pharmaceutical Industries Ltd. All rights reserved. GRANIX is a 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-40189 January 2014 This brief summary is based on TBO-003 GRANIX full Prescribing Information.

possibly pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen have not been highly effective in studies of treatment of PIP. Based on anecdotal evidence, the investigators postulated that the antihistamine loratadine could be an effective treatment for PIP. Disappointingly, loratadine failed to have an impact in this phase 2 pilot study. The prospective, randomized, placebo-controlled trial enrolled 227 patients undergoing pegfilgrastim treatment who were observed for the development of clinically significant PIP, which was defined as a score of 5 or higher on the Brief Pain Inventory instrument, with a 2-point or greater increase from baseline after an initial dose of pegfilgrastim. Of these, 65 patients developed PIP and were eligible for randomization, with 45 of them going on to be randomized to loratadine 10 mg or placebo daily for 7 days, initiated on day 1 of pegfilgrastim administration.

The investigators postulated that the antihistamine loratadine could be an effective treatment for PIP. Twenty patients dropped out of the study because they did not receive further pegfilgrastim, leaving 25 for evaluation (13 in the loratadine group and 12 in the placebo group). Patients randomized to loratadine achieved 59% improvement in PIP from baseline compared with 54.5% for placebo, which was not significantly different. Results remained the same after data were adjusted for use of rescue analgesics, including NSAIDs and nonNSAIDS. “This proves the value of confirming pilot studies. Based on this study, loratadine should not be used to treat PIP. However, a prophylactic study with loratadine versus naproxen use starting the day prior to pegfilgrastim is ongoing, and may guide a future role for this agent in the treatment of PIP,” Schwartz said. l References

1. Neulasta [package insert]. Thousand Oaks, CA: Amgen Inc; February 2014. 2. Moukharskaya J, Abrams DM, Khan FB, et al. Randomized phase II pilot study of loratadine for the prevention of bone pain caused by pegfilgrastim. Presented at: 50th Annual Meeting of the American Society of Clinical Oncology; May 30-June 3, 2014; Chicago, IL. Abstract 9628.

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Best Practices

Positive Patient Outcomes… Continued from cover at the University of California San Diego had previously described the development and initial achievement of a pharmacist-led outpatient palliative care practice conducted at a single academic comprehensive cancer center. The research team, composed of physicians and pharmacists, conducted physician-completed satisfaction surveys (n=11) and reported that the most valuable actions performed by pharmacists were time spent with patients without a physician present (91%) and recommendations for pain and symptom management (82%). The new research illustrates the effect on patients of the same pharmacist-physician collaboration. The role of pharmacists and the symptom management interventions they provide have been demonstrated in several studies of outpatient palliative and/ or supportive care practices. However, Ma and colleagues desired to expand the research to incorporate and evaluate patient outcomes from the pharmacist-led outpatient palliative care practice and found that the outcome was desirable. Their findings were presented in a poster at the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology 2014 annual meeting, held in Miami, Florida. Patient Composition, Pharmacist Training, and Data Analysis A retrospective data analysis was conducted on a cohort of 84 new adult

patients and 272 follow-up consultations from 2011 to 2012. Patients were referred by an oncologist and/or hematologist to the Doris A. Howell outpatient palliative care consultation service. New patients were allocated 60 minutes for a consultation, whereas existing patients arriving weekly to monthly for follow-up visits were given 30 minutes of consultation time. The majority of patients had a diagnosis of cancer (most commonly, gastrointestinal malignancy), and their consultations encompassed pain management, other physical symptoms, and conversations about goals of care. “The patients gave the pharmacists a whole host of other information. They felt like we were having a real discussion with them,” Ma said in an interview with The Oncology Pharmacist. “They enjoyed the pharmacists’ presence.” The pharmacists were allied health professional staff at the University of California San Diego Medical Center and had completed palliative medicine didac-

A pharmacist-physician collaboration in a palliative care outpatient setting was effective.

tic training and postgraduate training. Pharmacists in the study had independent prescriptive authority in accordance with California law, were licensed by the Drug Enforcement Administration, and held National Provider Identifier status. During the course of research, pharmacists were allowed to measure, start, stop, and/or adjust therapy for pain management, nausea, emesis, and any symptoms of side effects from drug treatment. The scope of the pharmacists’ prescriptive authority included Schedule II controlled substances for treatment of pain and other physical ailments. All treatment was performed under the supervision of a physician. “Pain scores can decrease for a variety of reasons that we don’t know of,” said Ma. “But we were able to establish a collaborative practice protocol which allowed us as pharmacists to see patients more consistently while being more aggressive toward modifying their therapy. If we started a patient on a pain medication, instead of saying, ‘See you in a month,’ we’d say we wanted to talk to them ‘in a couple of days.’ ” Ma and colleagues measured average pain score fluctuations at baseline (ie, initial visit) compared with follow-up visits. Frequencies were given as to the number of patients who reached a decrease in their pain score that was clinically relevant, or a 30% reduction in pain score compared with their first visit.

Significant Decrease in Pain Scores Researchers found that mean pain scores decreased significantly from follow-up .005). During visits 2 through 5 (P successive follow-up visits, the percentage of patients with a 30% decrease in pain score escalated. Patient-reported occurrence of constipation and nausea and vomiting lessened with follow-up appointments (P > .005). However, there was no change in patient-reported insomnia and dyspnea between the initial visit and follow-up visits (P > .005). Pharmacist-Physician Collaboration Found Successful Ma and colleagues concluded that a pharmacist-physician collaboration in a palliative care outpatient practice was effective in decreasing cancer patients’ pain symptoms and constipation. With continued follow-up visits, the patients in the study cohort sustained a 30% decrease in pain score. The researchers stated that “outpatient palliative care practices should include pharmacists, with prescribing authority, as part of a trans-disciplinary approach to care for patients with serious illness.” l Reference

Ma JD, Roeland EJ, Mitchell WM, et al. Patient outcomes of a pharmacist-physician collaboration in a palliative care outpatient setting. Presented at: 2014 Annual Meeting of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology; June 26-28, 2014; Miami, FL. Abstract 0151.

Noteworthy Numbers

Health Literacy As originally defined by researchers with the National Library of Medicine in 2000, health literacy is “the degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions.”1 In advance of the October observance of Health Literacy Month, here is additional information regarding this important issue. In 2003, more than 19,000 Americans aged 16 years and older participated in the National Assessment of Adult Literacy, which included, for the first time, a health literacy component. Health literacy was reported using 4 performance levels: Below Basic, Basic, Intermediate, and Proficient. Rates reported were2: • • • •

Intermediate 53% Basic 22% Below Basic 14% Proficient 11%

In 2010, the US Department of Health and Human Services released the National Action Plan to Improve Health Literacy, which includes 7 goals3: 1. D evelop and disseminate health and safety information that is accurate, accessible, and actionable. 2. P romote changes in the healthcare system that improve health information, communication, informed decision making, and access to health services. 3. Incorporate accurate, standards-based, and devel-

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opmentally appropriate health and science information and curricula in child care and education through the university level. 4. S upport and expand local efforts to provide adult education, English language instruction, and culturally and linguistically appropriate health information services in the community. 5. Build partnerships, develop guidance, and change policies. 6. I ncrease basic research and the development, implementation, and evaluation of practices and interventions to improve health literacy. 7. I ncrease the dissemination and use of evidence-based health literacy practices and interventions. On its Health Literacy website, the Centers for Disease Control and Prevention lists health literacy activities for 20 states.4 From July 1, 2009, through June 30, 2012, Rutgers University School of Nursing and the Ironbound

Community Corporation (ICC) collaborated on health literacy classes for non–English-speaking Latino immigrants in a Newark, New Jersey, neighborhood. The ICC held 6 sessions of Spanish-language health literacy classes, each lasting between 8 and 12 weeks. A total of 64 participants attended at least 80% of the classes, and most participants reported increased ability to access needed health services. About one-third of the agency’s staff were trained to identify and support clients with low health literacy, and the university updated its curriculum to include health literacy.5 In a recent small study of 65 patients and 30 nurses, results demonstrated that nurses were 6 times as likely to overestimate rather than underestimate patients’ health literacy.6 Sources 1. www.nlm.nih.gov/archive//20061214/pubs/cbm/hliteracy.html. 2. http://nces.ed.gov/pubsearch/pubsinfo.asp?pubid=2006483. 3. http://www.health.gov/communication/hlactionplan/. 4. http://www.cdc.gov/healthliteracy/statedata/index.html. 5. http://www.rwjf.org/en/research-publications/find-rwjf-research/2014/05/ health-literacy-101-in-newark--n-j-.html. 6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814908/.

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The Academy of Oncology Nurse & Patient Navigators (AONN+) invites you to share your story of how cancer has affected you or a loved one. These stories will serve as a forum to build awareness and be a source of inspiration and reassurance to others. Select stories will be featured on the AONN+ website and in future issues of the Journal of Oncology Navigation & Survivorship ®.

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August 2014 I VOL 7, NO 3

Conference News: AVBCC

Worksite Pharmacy… Continued from page 7 hypertension, or chronic obstructive pulmonary disease is diagnosed with cancer, management of comorbidities is essential to help patients avoid costly hospital admissions. “Sometimes these other conditions get overlooked,” said Raulerson. “The role we can play is helping them to continue to manage those conditions, because you don’t want that diabetic person to end up in the ER or admitted to the hospital and either delay their cancer therapy or lessen it.” Worksite pharmacists are able to assist cancer patients with preventive care and triage, ensuring that high-risk oncology patients receive proper vaccinations. Teaching patients how and when to take their medications increases adherence, resulting in lower morbidity rates. Adverse events are common for oncology patients. Onsite pharmacists can help patients recognize whether these are drug-related events or conditions of the disease, and they can often provide relief with over-the-counter treatment. In addition, they can determine the severity of the problem and refer the patient for appropriate treatment, thereby preventing the unnecessary use of resources. Raulerson said, “I really think the role of the onsite pharmacist is leveraging that patient relationship and helping that patient navigate the complexities of oncology treatment.” Florencio Calderon, PharmD, BCPS, clinical director at Walgreens, addressed the difficulties employers face in determining how to provide quality cancer treatment for their employees in a cost-effective manner. “I work with our employers in terms of understanding where some of the challenges are, and one of the biggest challenges is oncology,” Calderon said. Calderon identified factors employers must consider when making employee healthcare decisions: • Evidence-based care versus avoidable costs: Choosing quality care while also determining costs that may be avoidable can be difficult. • Transparency of outcomes: Employers must examine the outcomes from their own programs as well as the outcomes that are available through medical data. • Site-of-care optimization and medical benefit management: “Site-of-care disparity in terms of cost has a significant impact, not only on the employer, but to the patient, because a lot of the benefit designs have a sharing of the cost.” • Alignment of incentives and optimizing benefit design: The benefit design should provide both the appropriate quality of care and access to that care. • Ancillary care management: Providing access, coordination, and management for ancillary care is critical.

August 2014 I VOL 7, NO 3

• Provider and network contracting: “There’s an opportunity to create high-value networks and to have care that exemplifies a best practice approach.” Oncology care further complicates employers’ healthcare decisions. In 2013, there were an estimated 1.6 million

THIRD

new cancer cases in the United States.4 “When we think about the impact to the workforce, the compelling piece is that 10% of healthcare costs are attributed to 1.6% of the impact population,” 5,6 Calderon noted. The rising incidence of cancer, coupled with an aging workforce population,

means that managing this disease will be a growing challenge for employers. “Just from an ability to have benefits to maintain treatment, these employees will continue to be active in the workforce. It becomes important in terms of how we are thinking of managing these patients,” said Calderon.

ANNUAL CONFERENCE

GLOBAL BIOMARKERS Clinical Approaches to CONSORTIUM Targeted Technologies ™

™

October 31 – November 1, 2014 • Marriott Marquis • San Francisco, CA

CONFERENCE CHAIRS Jorge E. Cortes, MD

Chair, CML and AML Sections D.B. Lane Cancer Research Distinguished Professor for Leukemia Research Department of Leukemia, Division of Cancer Medicine The University of Texas MD Anderson Cancer Center Houston, TX

Roy S. Herbst, MD, PhD

Ensign Professor of Medicine Professor of Pharmacology Chief of Medical Oncology Director, Thoracic Oncology Research Program Associate Director for Translational Research Yale Cancer Center, New Haven, CT

CONFERENCE OVERVIEW

The only global meeting dedicated to advancing the understanding of value and clinical impact of biomarker research in oncology. Guided by the expertise of leaders in this ﬁeld, participants will receive a thorough understanding of the current and future landscape of the relevance of tumor biomarkers and how to effectively personalize cancer care in the clinical setting.

TARGET AUDIENCE

This activity has been designed to meet the educational needs of medical oncologists and hematologists, pathologists, geneticists, advanced practice oncology/hematology nurses, research nurses, clinical oncology pharmacists, and genetic counselors involved in the management of patients with solid cancers or hematologic malignancies, and interested in the use of molecular biomarkers to help optimize patient care. Research scientists interested in the ﬁeld of molecular biomarkers in oncology are also invited to participate.

DESIGNATION OF CREDIT STATEMENTS ACCREDITATION STATEMENT

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Postgraduate Institute for Medicine and Center of Excellence Media, LLC. The Postgraduate Institute for Medicine is accredited by the ACCME to provide continuing medical education for physicians.

CREDIT DESIGNATION

The Postgraduate Institute for Medicine designates this live activity for a maximum of 9.5 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICANS WITH DISABILITIES ACT

Event staff will be glad to assist you with any special needs (ie, physical, dietary, etc). Please contact Linda Sangenito prior to the live event at (732) 992-1520.

DISCLOSURE OF CONFLICTS OF INTEREST

Postgraduate Institute for Medicine (PIM) requires instructors, planners, managers, and other individuals who are in a position to control the content of this activity to disclose any real or apparent conﬂict of interest (COI) they may have as related to the content of this activity. All identiﬁed COI are thoroughly vetted and resolved according to PIM policy. The existence or absence of COI for everyone in a position to control content will be disclosed to participants prior to the start of each activity. Jointly provided by Postgraduate Institute for Medicine and Center of Excellence Media, LLC

EDUCATIONAL OBJECTIVES

After completing this activity, the participant should be better able to: • Assess emerging data and recent advances in the discovery of molecular biomarkers on the management of patients with solid tumors and hematologic malignancies •

Discuss the role of molecular biomarkers in designing personalized therapy for patients with solid tumors and hematologic malignancies

•

Outline the practical aspects and value-based considerations of integrating molecular biomarkers into everyday clinical practice in the treatment of patients with cancer

This activity is supported, in part, by independent educational grants from Lilly. For further information concerning Lilly grant funding visit www.lillygrantoffice.com. This activity is also supported, in part, by an educational grant from Prometheus. Current at time of printing.

SUBMIT AN ABSTRACT BY SEPTEMBER 5, 2014 Submit an abstract for the Third Annual Global Biomarkers Consortium. This is an opportunity to share research, programs, and results with your peers. This session will facilitate communication among the various professionals and programs to advance the knowledge of all our members and those in attendance.

www.globalbiomarkersconsortium.com/conference/abstracts

www.TheOncologyPharmacist.com

Conference News: AVBCC

The use of oral oncolytics is becoming more prevalent in cancer treatment. These drugs allow patients to be managed as outpatients. “They give them the flexibility to still have a sense of a ‘normal’ life. I say that in quotes because these drugs do come with toxicity,” Calderon explained.

Toxicity creates problems like adverse effects that can lead to nonadherence. “If a patient’s not adherent, we’re going to have a disastrous outcome in many ways, not just from a patient perspective with their disease, but from a cost perspective as well, because that patient will be hospitalized and will incur higher costs,”

AGENDA*

FRIDAY, OCTOBER 31

• Myeloid hematologic malignancies – Jorge E. Cortes, MD • Chronic lymphocytic leukemia – William Wierda, MD, PhD • Multiple myeloma – Sagar Lonial, MD • Lymphoma – Anas Younes, MD

7:00 am - 12:00 pm Registration 11:45 am - 2:15 pm Product Theaters 2:15 pm - 2:30 pm

Break

2:30 pm - 2:40 pm

Welcome to the Third Annual Conference of the Global Biomarkers Consortium — Opening Remarks

2:40 pm - 4:15 pm

General Session I: Cancer Care in the Era of Molecular Biomarkers • Personalized medicine in oncology: therapeutic advances from cytotoxic chemotherapy to molecularly targeted agents – Razelle Kurzrock, MD • Understanding cancer at the molecular level – Caroline Robert, MD, PhD • Standardization of molecular biomarker testing – Mark Sausen, MD • Implications of molecular diagnostics on clinical trial design – John J. Wright, MD, PhD Question & Answer Session

4:15 pm - 4:30 pm

Break

4:30 pm - 5:30 pm

General Session II - Part 1: Incorporating Molecular Biomarkers into the Therapy of Solid Tumors — Case Studies on “How I Treat” • Melanoma – Sanjiv S. Agarwala, MD • Breast cancer – Hope Rugo, MD Question & Answer Session

5:30 pm - 7:00 pm

Welcome Reception and Exhibits

11:05 am - 12:00 pm Keynote Lecture: Markers of Resistance to Targeted Therapies – Alberto Bardelli, PhD Question & Answer Session 12:00 pm - 1:00 pm Meet the Experts and Lunch in the Exhibit Hall 1:00 pm - 1:15 pm

Break

1:15 pm - 2:00 pm

Tumor Board Breakout Sessions • Attendee cases in solid tumors • Attendee cases in hematologic malignancies

2:00 pm - 2:15 pm

Break

2:15 pm - 3:30 pm

General Session IV: Molecular Biomarkers for the Early Detection of Cancer: Are They Ready for Prime Time? • Developing and validating biomarkers via the Early Detection Research Network (EDRN-NCI) – Sudhir Srivastava, PhD, MPH • Beyond PSA: novel molecular biomarkers for prostate cancer – Mark Rubin, MD • Airway biomarkers for lung cancer detection in the post-NLST era – Avi Spira, MD, MSc • Early detection biomarkers for breast cancer – Karen Anderson, MD, PhD Question & Answer Session

3:30 pm - 3:45 pm

Break

3:45 pm - 4:00 pm

Keynote Lecture: Actionable Genomic Alterations in Oncology – Phil Stephens, PhD

4:00 pm - 4:50 pm

General Session V: Regulatory and Economic Aspects of Personalized Medicine in Oncology • Understanding the regulatory aspects of personalized medicine in oncology – Andrew Stainthorpe, PhD • A debate on health economics and molecular biomarkers: can we afford personalized medicine in oncology? – Gary Johnson, MD, MS, MBA, and Ken Schaecher, MD, FACP, CPC Question & Answer Session

4:50 pm - 5:00 pm

Closing Remarks

SATURDAY, NOVEMBER 1 7:00 am - 8:00 am

Product Theater

8:00 am - 8:15 am

Break

8:15 am - 8:30 am

Review of Friday’s Presentations and Preview of Today

8:30 am - 9:30 am

General Session II - Part 2: Incorporating Molecular Biomarkers into the Therapy of Solid Tumors — Case Studies on “How I Treat” • Melanoma – Sanjiv S. Agarwala, MD • Colorectal cancer – Axel Grothey, MD Question & Answer Session

9:30 am - 9:45 am

Break

9:45 am - 11:05 am General Session III: Incorporating Molecular Biomarkers into the Therapy of Hematologic Malignancies — Case Studies on “How I Treat”

Calderon said. Walgreens Oral Oncology Cycle Management was created to manage the care of patients taking oral oncolytics. Calderon explained, “This came to fruition because patients are being managed, more and more, on an outpatient basis, and these drugs have a high toxicity

range.” The program was established to create more intensive interactions with patients to (1) enhance the understanding, acceptance, and adherence of the patient to the medication, and (2) identify opportunities to manage, over the counter, any drug intolerance or toxicities the patient may experience, or assess the need for triage to the oncologist or the emergency department. The implementation of this program saved $1374 per patient in reduced waste and reduced hospitalization combined,7 Calderon said. At the same time, it improved the quality of care for the patient. l References

1. Boress L, Calderon F, Raulerson B. Employer and payer perspectives on cancer site of care: oncology infusion and alternative sites. Presented at: 4th Annual Conference of the Association for Value-Based Cancer Care; May 6-9, 2014; Los Angeles, CA. 2. NEHI research shows patient medication nonadherence costs health care system $290 billion annually [press release]. Cambridge, MA: New England Healthcare Institute. August 11, 2009. http://www. nehi.net/news/344-nehi-research-shows-patient-medi cation-nonadherence-costs-health-care-system-290-bil lion-annually/view. Accessed July 7, 2014. 3. Patwardhan A, Duncan I, Murphy P, et al. The value of pharmacists in health care. Popul Health Manag. 2012;15(3):157-162. 4. American Cancer Society. Cancer Facts & Figures 2013. Atlanta, GA: American Cancer Society; 2013. http://www.cancer.org/acs/groups/content/@epidemi ologysurveilance/documents/document/acspc-036845. pdf. Accessed July 7, 2014. 5. Pyrillis R. Cancer poses a growing challenge to employers. Workforce website. http://www.workforce. com/articles/cancer-poses-a-growing-challenge-to-em ployers. Published February 14, 2013. Accessed July 7, 2014. 6. Fitch K, Pyenson B. Cancer Patients Receiving Chemotherapy: Opportunities for Better Management. http://publications.milliman.com/research/health-rr/ pdfs/cancer-patients-receiving-chemotherapy.pdf. New York, NY: Millman, Inc; March 30, 2010. 7. Khandelwal N, Duncan I, Ahmed T, et al. Impact of clinical oral chemotherapy program on wastage and hospitalizations. Am J Manag Care. 2011;17(5 spec no): e169-e173.

Want to participate in TOP’s new poll? See page 6 for details.

*Agenda subject to change. GBC2014ConfAd Ksize_60914

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August 2014 I VOL 7, NO 3

Cancer Center Profile

Sequoia Regional Cancer Center… Continued from cover The Oncology Pharmacist spoke with Clint Brown, PharmD, about his role as oncology and pain management pharmacist at the Kaweah Delta Health Care District. He provides oncology and pain management expertise for cancer and noncancer patients treated within the district.

Clint Brown, PharmD

Tell me about your role at Kaweah and the Cancer Center. Clint Brown (CB): I wear 2 hats: I am the oncology pharmacist and 1 of 3 pain management pharmacists. The goal of cancer treatment is to focus on patient-specific outcomes and improve quality of life. I do that by trying to

maximize the efficacy of chemotherapy and minimize its toxicity. This is done by tailoring doses and regimens to the individual patient and maximizing both prophylactic medications and supportive measures. The same is true for pain control. We try to maximize efficacy and minimize toxicity by individualized dosing of pain medications utilizing a multimodal approach to limit pain. How did you become an oncology pharmacist/pain management specialist? CB: After completing a first-year pharmacy practice residency that focused on chronic pain management, I took a position with Kaweah as a clinical pharmacist, helping to provide pain management for acute palliation and hospice patients. At the same time, a position became available for an oncology pharmacist. Feeling that I could serve the pain needs of our cancer patients, I filled the position, and now I do both. About 9 months ago, we implemented a pharmacy-driven pain management service and expanded it throughout the entire hospital in an effort to better manage pain and prevent opioid-associated adverse events.

What is the main challenge of your job? CB: My biggest challenge is seeing the emotional and physical struggles of the patients and their families as they undergo the treatment process for their cancer. We spend a great deal of time with them in an effort to help shoulder that burden by being an expert resource with regard to their medications, how they work, how to take them, what to expect, and how to mitigate any side effects.

other examples too. I am hopeful that the newly identified metastasis-suppressor gene for prostate cancer will lead to better targeted treatments and improved outcomes.

What about your rewards? CB: Being able to spend a lot of time with the patients. They are incredible. My main reward is getting to know that patient well and being able to help him/ her overcome and beat cancer. That doesn’t happen for all patients, but when it does it is very rewarding.

What advice would you give to a person entering this field? CB: Do not shy away from working as an oncology pharmacist. You get to meet the most incredible and courageous people in the world. Even though the regimens can be complex and outcomes may not always be ideal, oncology pharmacy provides the best opportunity to do what we are good at, which is educating doctors, nurses, the multidisciplinary team, and patients themselves about the medications they need to take. We can help promote adherence, maximize benefits, and mitigate toxicity.

What are you excited about in the field of oncology? CB: The targeted therapies are now turning once-fatal cancers into chronic manageable disease states that patients live with rather than die from. Some examples are imatinib for gastrointestinal stromal tumor and trastuzumab for HER2-positive breast cancer. There are

What would you be doing if you won the lottery? CB: I would stay in the field of oncology. I love the interaction with patients and being able to help them. Outside of that, I would compete in triathlons and spend more time outdoors with my wife and my 5-year-old and 3-year-old sons. l

Conference News: ASCO Continued from page 13

Goserelin Preserves Ovarian Function in Premenopausal Women With Breast Cancer The addition of goserelin to chemotherapy was shown to preserve ovarian function, fertility, and the ability to have a successful pregnancy in premenopausal women with hormone receptor–negative (HR–) early breast cancer, according to results of the Prevention of Early Menopause Study (POEMS), an international Intergroup trial coordinated by the Southwest Oncology Group. The study was presented as a late-breaking oral abstract during the American Society of Clinical Oncology 2014 annual meeting. “This is the first demonstration of fertility prospects and more successful pregnancies in women with breast cancer. Premenopausal women with HR– breast cancer should be offered this option,” stated lead author Halle Moore, MD, of the Cleveland Clinic in Ohio. Goserelin and other luteinizing hormone-releasing hormone (LHRH) analogs shut down ovarian function and put patients in a postmenopausal state. The goal of using this drug is to protect the ovaries during chemotherapy. Ovarian failure was the primary end point of the study and was defined as amenorrhea for the prior 6 months and postmenopausal levels of follicle-stimulating hormone (FSH). The investigators also assessed disease-free survival (DFS) and overall survival (OS). The study, which was conducted from February 2004 to May 2011, randomized 257 premenopausal women (median age, 38 years) with stage I-IIIA HR– breast cancer to treatment with cyclophos-

August 2014 I VOL 7, NO 3

phamide-containing chemotherapy (standard arm) or the same chemotherapy plus goserelin given as monthly injections starting 1 week before chemotherapy. More than 90% got anthracycline-containing chemotherapy, and cancer stage distribution was similar in the 2 arms. Endocrine toxicity was twice as high in the goserelin arm compared with chemotherapy and included hot flashes, mood swings, dry vagina, and headache.

Halle Moore, MD

At 2 years, ovarian failure occurred in 22% of the chemotherapy arm versus 8% of the goserelin arm (P = .04). Regardless of stratification factors, goserelin achieved a lower rate of ovarian failure. The 2-year rate of ovarian dysfunction was also significantly lower in the goserelin arm: 33% with standard chemotherapy versus 14% with goserelin (P = .03). Goserelin did not increase the risk of any complications or terminations of pregnancy com-

pared with chemotherapy alone. Eighteen patients in the standard chemotherapy arm and 25 in the goserelin arm tried to become pregnant. Women in the goserelin arm were about 2.5 times more likely to conceive. Successful pregnancies were reported in 12 patients (11%) in the standard chemotherapy arm and 22 (21%) in the goserelin arm. Live births were reported in 8 patients in the standard chemotherapy arm (7%, 12 babies) and 15 patients in the goserelin arm (15%, 18 babies; P = .03). Goserelin did not increase the risk of any complications or terminations of pregnancy compared with chemotherapy alone. Unexpectedly, goserelin also improved DFS and OS. The 4-year DFS rate was 78% in the standard chemotherapy arm and 89% in the goserelin arm (P = .04), and 4-year OS was 82% versus 92%, respectively (P = .06). The study had some limitations, however, including missing data for 38% of patients, but Moore said this is the largest randomized study of LHRH agonist use for ovarian protection in HR– breast cancer, and it is the most informative study reporting pregnancy outcomes with an LHRH analog during chemotherapy. l Reference

Moore HCF, Unger JM, Phillips K-A, et al. Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy (CT) to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer: an international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance). Presented at: 50th Annual Meeting of the American Society of Clinical Oncology; May 30-June 3, 2014; Chicago, IL. Abstract LBA505.

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August 2014 I VOL 7, NO 3

THIRD ANNUAL

WORLD CUTANEOUS MALIGNANCIES CONGRESS

™

October 29 – October 31, 2014 • Marriott Marquis • San Francisco, CA A 2-day congress dedicated to informing, educating, and fostering the exchange of clinically relevant information in the ﬁeld of cutaneous malignancies on topics in melanoma, basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, and cutaneous T-cell lymphoma.

CONFERENCE CHAIR

WORLD CUTANEOUS MALIGNANCIES CONGRESS

Sanjiv S. Agarwala, MD Bethlehem, PA

PROGRAM COMMITTEE

Axel Hauschild, MD Kiel, Germany

Paul Nghiem, MD, PhD Seattle, WA

Pierluigi Porcu, MD Columbus, OH

Aleksandar Sekulic, MD, PhD Scottsdale, AZ

™

TARGET AUDIENCE

This educational initiative is directed toward medical and surgical oncologists, dermatologists, and radiation oncologists involved in the treatment of patients with cutaneous malignancies. Fellows, nurse practitioners, nurses, physician assistants, pharmacists, researchers, and other healthcare professionals interested in the treatment of cutaneous malignancies are also invited to participate.

EDUCATIONAL OBJECTIVES

After completing this activity, the participant should be better able to: • Review the molecular biology and pathogenesis of malignant melanoma, CTCL, BCC, and MCC, including how they relate to targeted therapy • Describe how to tailor therapeutic options and optimal sequencing for individual patients with melanoma, CTCL, BCC, and MCC • Utilize emerging data and recent advances with new molecular targets for the treatment of patients with metastatic melanoma, CTCL, BCC, and MCC into clinical practice • Identify new technologies for the prevention and early detection of cutaneous malignancies

PHYSICIAN CONTINUING MEDICAL EDUCATION

Accreditation Statement This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Postgraduate Institute for Medicine and Center of Excellence Media. The Postgraduate Institute for Medicine is accredited by the ACCME to provide continuing medical education for physicians.

CREDIT DESIGNATION*

The Postgraduate Institute for Medicine designates this live activity for a maximum of 9.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. *This CME/CE activity complies with all requirements of the federal Physician Payment Sunshine Act. If a reportable event is associated with this activity, the accredited provider managing the program will provide the appropriate physician data to the Open Payments database.

DISCLOSURE OF CONFLICTS OF INTEREST

Postgraduate Institute for Medicine (PIM) requires instructors, planners, managers, and other individuals who are in a position to control the content of this activity to disclose any real or apparent conﬂict of interest (COI) they may have as related to the content of this activity. All identiﬁed COIs are thoroughly vetted and resolved according to PIM policy. The existence or absence of COIs for everyone in a position to control content will be disclosed to participants prior to the start of each activity.

AMERICANS WITH DISABILITIES ACT

Event staff will be glad to assist you with any special needs (ie, physical, dietary, etc). Please contact Linda Sangenito prior to the live event at 732-992-1520.

This activity is jointly provided by Postgraduate Institute for Medicine and Center of Excellence Media, LLC.

For more information please visit www.CutaneousMalignancies.com www.TheOncologyPharmacist.com

August 2014 I VOL 7, NO 3

AGENDA*

WEDNESDAY, OCTOBER 29 3:00 pm - 7:00 pm

Registration

5:30 pm - 7:30 pm

Welcome Reception/Exhibits

THURSDAY, OCTOBER 30 6:45 am - 9:15 am

Breakfast Product Theaters

9:15 am - 9:30 am

Break

9:30 am - 9:45 am Welcome to the Third Annual World Cutaneous Malignancies Congress - Setting the Stage for the Meeting – Sanjiv S. Agarwala, MD 9:45 am - 11:45 am General Session I The Molecular Biology of Cutaneous Malignancies Implications for Personalized Therapy • Understanding the molecular biology of malignant melanoma: a clinical perspective – Antoni Ribas, MD • The molecular basis of basal cell carcinoma (BCC) – James MacDonald • Cutaneous T-cell lymphoma (CTCL): molecular aspects of disease development and response to targeted agents – Anjali Mishra, PhD • Immunologic characterization of tumor cells in CTCL: application to clinical practice – Rachel Clark, MD, PhD • Virus-positive and virus-negative Merkel cell carcinoma (MCC): implications for the clinician – Isaac Brownell, MD, PhD Question & Answer Panel Discussion

• Ongoing clinical studies in BCC – Aleksandar Sekulic, MD, PhD • New systemic therapies in CTCL: beyond the old paradigms – Steve Horowitz • Emerging treatment options in MCC: chemotherapy and alternative approaches for metastatic disease – Shailender Bhatia, MD Question & Answer Session 4:35 pm - 5:15 pm Tumor Board Breakout Sessions • Attendee cases in malignant melanoma • Attendee cases in BCC • Attendee cases in CTCL and MCC 5:15 pm - 7:00 pm

FRIDAY, OCTOBER 31

Cocktail Reception/Exhibits

7:00 am - 8:00 am

Breakfast

8:00 am - 8:15 am

Break

8:15 am - 8:30 am Review of Thursday’s Presentations and Preview of Today’s Sessions – Sanjiv S. Agarwala, MD

11:45 am - 12:00 pm Break

8:30 am - 9:30 am General Session IV Prevention and Early Detection • Early detection of primary tumors in melanoma – Susan M. Swetter, MD • A new serologic assay for early detection of recurrent MCC – Paul Nghiem, MD, PhD • An update on the SCREEN trial: skin cancer screening in Germany – Axel Hauschild, MD Question & Answer Session

12:00 pm - 1:00 pm

9:30 am - 9:45 am

Meet the Experts/Lunch in the Exhibit Hall

1:00 pm - 2:15 pm General Session II Current Treatment Algorithms in Cutaneous Malignancies • Current approaches to therapy in malignant melanoma: the US perspective – Antoni Ribas, MD • Current approaches to therapy in malignant melanoma: the EU perspective – Axel Hauschild, MD • Current treatment options for advanced BCC – Karl Lewis, MD • Current treatment options in CTCL – Pierluigi Porcu, MD • Update on NCCN guidelines for the management of MCC – Christopher K. Bichakjian, MD 2:15 pm - 2:30 pm

Break

2:30 pm - 2:50 pm Keynote Debate International Focus on Melanoma: Case Presentation Followed by US vs EU vs Latin America Debate on Therapy – Sanjiv S. Agarwala, MD; Héctor Martínez Saíd, MD; Axel Hauschild, MD 2:50 pm - 4:35 pm General Session III Emerging Therapies, Combos, and Targeted Agents • Changing arena of adjuvant therapy in malignant melanoma – Reinhard Dummer, MD, PhD

Break

9:45 am - 11:10 am General Session V What’s Hot in New Drugs and Clinical Trial Data • Anti–PD-1 antibodies ± ipilimumab in melanoma – Caroline Robert, MD, PhD • Real-world management of BCC: the RegiSONIC study – Jean Tang, MD, PhD • New data on lymphoma biology with applications to CTCL – Leandro Cerchietti, MD • Rationale and status of immune targeted therapies for MCC – Isaac Brownell, MD, PhD Question & Answer Session 11:10 am - 11:25 am Keynote Panel Discussion Is There a Role for “Conventional Therapies” for Cutaneous Malignancies in the Era of Targeted Agents? – Sanjiv S. Agarwala, MD; Axel Hauschild, MD; Paul Nghiem, MD, PhD; Pierluigi Porcu, MD; Aleksandar Sekulic, MD, PhD 11:25 am - 11:30 am

Closing Remarks – Sanjiv S. Agarwala, MD

*Agenda subject to change.

For full faculty information please visit www.CutaneousMalignancies.com

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August 2014 I VOL 7, NO 3

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