IASLC Lung Cancer News - V1, N1

LUNG CANCER

V1 / N1 / APRIL 2016

NEWS

FOR THORACIC SPECIALISTS www.iaslc.org

INSIDE 2

4th AACR-IASLC International Joint Conference Highlights

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16th Annual Meeting on Targeted Therapies for Lung Cancer Highlights

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FDA Corner Best of the 16th WCLC Athens Afatinib Outperforms Gefitinib in Advanced NSCLC Update on Checkpoint Inhibitors NCI Corner Lung Cancer CT Screening Clinicians and Tobacco Lung Cancer Survivor Wins Trip

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Perspective: When Breath Becomes Air by Kalanithi

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Nurses Treating Lung Cancer

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Names and News

Lung Cancer Meetings Calendar

Fred R. Hirsch, MD, PhD IASLC CEO

Welcome, IASLC Lung Cancer News!

IASLC is proud to launch the IASLC Lung Cancer News. Lung cancer is a major health issue all over the world, with roughly 1.6 million patients diagnosed globally every year, including 225,000 new patients every year just in the US. In light of the progress happening these days in the prevention and treatment of this disease, from screening to novel treatments for advanced disease, including personalized therapy, we see a strong continued on page 2

I N T E R N AT I O N A L A S S O C I AT I O N F O R T H E S T U D Y O F L U N G C A N C E R

From the Editor / Corey J. Langer, MD, FACP Greetings.

It is my privilege to introduce the IASLC Lung Cancer News (ILCN). I will be serving as Editor with the able assistance of my Associate Editors, Fabrice Barlesi, MD from Europe and Caicun Zhou, MD from Asia. ILCN is a new tabloid publication that will highlight updates on thoracic malignancy research, including diagnostics, screening, tobacco control, therapeutic interventions, quality of life, symptom management, and survivorship. This tabloid will acknowledge the complex interplay that exists between these investigational realms and between all stakeholders in the research and care of individuals with thoracic cancers, and will feature expert commentary from thoracic oncology leaders, industry, and regulators.

The target audience for this publication encompasses researchers, physicians, and other specialists, including allied health professionals, involved in the care of patients with thoracic malignancy.

ILCN is structured to present the most recent and noteworthy lung cancer-related information worldwide; in addition, themed issues will be planned around particular topics or meetings, and we will not shy away from ongoing controversies and debates. We have twin goals of facilitating professional development and improving patient care and

research, and ultimately clinical outcome.

Year 1 of the publication will consist of 1 issue each quarter, 16 pages each, and will be distributed in print and electronically to US and international thoracic cancer specialists. During year 2, we plan to transition to an issue every two months, with up to 32 pages each.

Each issue will include, but will not be limited to, the following topics: • Meeting Highlights and Previews • Expert Corner • NCI Corner • FDA Corner • Global Research Spotlights • Recent International Drug Approvals • Lung Cancer Screening • Tobacco Control and Smoking Cessation • Navigating Therapeutic Controversy continued on page 11

Welcome from David Carbone, MD, PhD, IASLC President These are exciting times in lung cancer treatment and research, but there is still a lot of room for improvement in propagating these discoveries to all lung cancer patients around the world, and converting responses to cures; in this context, as President of the International Association for the Study of Lung Cancer, I am pleased to welcome you to the first issue of IASLC Lung Cancer News.

Important issues for lung cancer experts and health care providers worldwide will be covered in IASLC Lung Cancer News, spanning all specialties and ranging from the role of screening and early detection to the latest treatment approaches and management strategies for advanced disease. continued on page 11

M eeting pre v iew H I G H L I G H T S

IASLC and ESMO Present 6th European Lung Cancer Conference

By Nicola M. Parry, DVM

From April 13-16, 2016, the International Association for the Study of Lung Cancer (IASLC) and the European Society for Medical Oncology (ESMO) will once again join forces to host the 6th European Lung Cancer Conference (ELCC) at Palexpo in Geneva, Switzerland. This meeting is a collaborative effort of key multidisciplinary societies representing thoracic oncology specialists—all working to advance science, provide education, and enhance the practice of lung cancer specialists worldwide. It plays a

key role in providing an updated overview of prevention, screening, diagnosis, and treatment of lung cancer, as well as results of basic, clinical, and translational research.

Now held annually, ELCC is an important conference in Europe for all clinicians involved in the diagnostic workup and treatment of lung cancer and other thoracic malignancies. The conference attracts a diverse audience that includes medical oncologists, radiotherapists, thoracic surgeons, respiratory

physicians, interventional radiologists, and pathologists. In this way, the meeting aims to foster productive multidisciplinary interaction among specialists in order to strengthen an integrated approach to diagnosis and treatment of lung and other thoracic cancers.

During the 4-day program, an internationally renowned faculty of thoracic oncology specialists will present updates on a variety of topics that address the scientific and educational needs of continued on page 6

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IASLC Lung Cancer News / APRIL 2016

M eeting H ighlights

4th AACR-IASLC International Joint Conference:

Lung Cancer Translational Science from the Bench to the Clinic

By Nicola M. Parry, DVM

The 4th conference driven by the dynamic collaboration of the International Association for the Study of Lung Cancer (IASLC) and the American Association for Cancer Research (AACR) took place January 4-7 at the Hard Rock Hotel in San Diego, California. Combining the strengths of both organizations, this annual international joint conference continues to attract a varied audience, including physicians and patient advocates, as well as scientists in basic, translational, and clinical fields of lung cancer research. By bringing together this diverse group of professionals each year, this meeting aims to promote scientific interaction and discussion of recent advances in lung cancer research and treatment, to address important needs in these key areas.

The focus of this year’s meeting was “Lung Cancer Translational Science from the Bench to the Clinic.” Approximately 250 attendees heard about the most recent advances across the spectrum of lung cancer research. During the 4-day program, 7 plenary sessions covered a range of topics that included early detection and prevention, immunotherapy, drug resistance, and novel targets and pathways; one of these sessions was devoted to presentations of highly rated abstracts, many by early-career researchers. Another session—“How Advocacy is Driving Science”—discussed the role of advocates and advocacy organizations in driving lung cancer science, and highlighted how patient advocates, scientists, and clinicians collaborate to fuel progress against lung cancer. Topics featured

in concurrent sessions included animal models, stem cells, diagnostics and biomarkers, and hot topics in radiation oncology. Throughout the conference, attendees shared updates from the meeting on social media using the dedicated #Lung16 hashtag.

“

In this session, we heard about exciting new avenues in small cell lung cancer, some of which have led to clinical trials that have had a real impact on patients with this disease.

—Alice T. Shaw, MD, PhD

” According to conference chairpersons Karen L. Kelly, MD (UC Davis Comprehensive Cancer Center, Sacramento, California) and Alice T. Shaw, MD, PhD (Massachusetts General Hospital Cancer Center, Boston, Massachusetts), this year’s meeting was an “absolute success” with many highlights. In particular, they emphasized how the first session of the meeting, on small cell lung cancer, showcased how basic research can be translated into new and effective therapeutic strategies. “Until now, little progress has been made in small cell lung cancer, with the same chemotherapy regimens used over the last few decades,” noted Dr. Shaw. However, “in this session, we heard about exciting new avenues in small cell lung cancer,

Welcome from page 1

need to initiate a forum to disseminate this knowledge to all individuals who deal with lung cancer patients, whether they are in academia or in the community, and to the public. We have also identified the need to have experts discuss the latest scientific advances and to put these advances into a patient/public perspective. As an “academic” organization that includes lung cancer experts from all medical disciplines and from all regions of the world, we believe it is both an obligation and an opportunity to offer this information to a broader audience, so that lung cancer patients, their families, and the caregivers can appreciate the latest developments as soon as possible with the experts’ perspective. It is our hope that the IASLC Lung Cancer News will fulfill this mission and will help optimize care for all lung cancer patients whether they are in the US or abroad; in so doing, we strongly believe that this new initiative will help bring hope and optimism to patients with lung cancer, so many of whom desperately need it.

It is also our hope that the IASLC Lung Cancer News will help disseminate new perspectives and updated information to the public, so together we can fight and defeat this disease.✦ —Fred R. Hirsch, MD, PhD Chief Executive Officer, IASLC

some of which have led to clinical trials that have had a real impact on patients with this disease,” she said.

Updated results were also presented from several studies, including preliminary findings from the ongoing Phase I/II Xalt2 trial on the investigational tyrosine kinase inhibitor (TKI), X-396, in patients with anaplastic lymphoma kinase positive (ALK+) advanced non-small cell lung cancer (NSCLC). Dr. Karen L. Reckamp (City of Hope Comprehensive Cancer Center) presented the safety and efficacy data, which continue to demonstrate that X-396 has promising activity in patients with ALK+ NSCLC. Data were also presented from a study involving LL-067, an epidermal growth factor receptor (EGFR) inhibitor currently in development. According to Nicholas Cacalano, MD (University of California Los Angeles David Geffen School of Medicine), study findings so far have shown that LL-067 accumulates in the brain and inhibits the growth of metastatic NSCLC. Clinical trials involving LL-067 are expected to begin this year.

In another presentation, Diane Legg, a lung cancer patient and survivor, shared a patient’s perspective on the impact of basic and clinical research on patient care. Diane, who has advanced EGFR mutant lung cancer, reflected on the remarkable path she has taken since her diagnosis over 10 years ago. “She discussed how important it was for her to pursue a clinical trial in order to access new therapies that could be more effective than standard therapy,” said Dr. Shaw.

Diane participated in a clinical trial of a novel combination of targeted therapy and immunotherapy, and during her presentation, she also “reflected on how clinical trials can, on the flip side, expose patients to unexpected side effects that limit the potential benefit of the treatment,” added Dr. Shaw.

Reflecting on the success of the conference, Dr. Shaw emphasized how it “brought together the various disciplines who are invested in finding a cure for lung cancer—basic scientists, translational scientists, clinicians, [and] drug makers.” She also noted the attendance of many trainees who are committed to studying lung cancer in order to find the next breakthroughs. “The meeting provided a great opportunity for us not only to learn the latest advances from each other, but also to build collaborations,” Dr. Shaw concluded.✦

LUNG CANCER

NEWS

I N T E R N AT I O N A L A S S O C I AT I O N F O R T H E S T U D Y O F L U N G C A N C E R

Editor Corey J. Langer, MD, FACP Associate Editors Fabrice Barlesi, MD and Caicun Zhou, MD IASLC CEO Fred R. Hirsch, MD, PhD managing Editor and Publisher Deb Whippen, Editorial Rx, Inc. Production Director Doug Byrnes Graphic Designer Amy Boches, biographics

IASLC Lung Cancer News is published quarterly by the International Association for the Study of Lung Cancer (IASLC). IASLC Headquarters is located at 13100 East Colfax Avenue, Unit 10, Aurora, CO, 80011, US. Purpose and Audience: IASLC Lung Cancer News features news about lung cancer research, patient care, tobacco control, and expert commentary from lung cancer leaders.

The target audience for this publication is physicians and other specialists involved in the research and treatment of patients with lung cancer and other thoracic oncologic disorders.

Correspondence: Address correspondence to Corey J. Langer, MD, FACP, Editor, c/o editor@iaslclungcancer.net.

Change of Address: Postmaster send address changes to IASLC Lung Cancer News, c/o IASLC Headquarters, 13100 East Colfax Avenue, Unit 10, Aurora, CO, 80011, US. Subscription: To initiate or cancel a subscription to IASLC Lung Cancer News or to update your mailing address, please email membership@ iaslc.org or call +1-720-325-2956.

Advertising: For information on advertising rates or reprints, contact Kevin Dunn, Cunningham Associates, 201-767-4170, kdunn@cunnasso.com. All advertising is subject to acceptance by IASLC. IASLC is not responsible for the content of advertising and does not endorse any advertiser or its products or services.

Disclaimer: The ideas and opinions expressed in IASLC Lung Cancer News do not necessarily reflect those of the International Association for the Study of Lung Cancer. The mention of any product, service, or therapy in this publication should not be construed as an endorsement, and the Association accepts no responsibility for any injury or damage to person or persons arising out of or related to any use of material contained in this publication or to any errors or omissions.

IASLC Lung Cancer News / APRIL 2016

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M eeting H I G H L I G H T S

16th Annual Meeting on Targeted Therapies for Lung Cancer Leading experts in the biology, diagnosis and treatment of lung cancer met for 3 days in February 2016 at the 16th Annual Meeting on Targeted Therapies for Lung Cancer. Held from February 17-20 in Santa Monica, US, this work-in-progress meeting is an annual event sponsored by the IASLC and is designed to bring together translational researchers and lung cancer investigators to assess current areas of research and future directions.

The meeting focused on new ideas and developments in lung cancer research, including the latest advances in immunotherapy, immunotherapeutic combinations, and biomarkers for immunotherapy, as well as targetdelineated therapies, including EGFR

and ALK, with a new focus on acquired resistance.

The development of specific molecular treatments in lung cancer has led to a paradigm shift in thoracic oncology research for which meetings such as Targeted Therapies for Lung Cancer provide vital leadership. Conferences such as this annual event serve to catalyze and promote new ideas, and foster active collaboration between multiple academic institutions and industry. The educational design of Targeted Therapies for Lung Cancer is structured to provide an informal yet expert forum on research in progress.

Advances in various areas of research as well as disappointing results in other

areas were the subject of networking events throughout the meeting.

“The Santa Monica meetings provide a unique opportunity for thoracic oncology investigators from around the world

By Erik J. MacLaren, PhD

In 2015, the US Food and Drug Administration (FDA) approved an unprecedented 7 new drugs or new uses for drugs for patients with lung cancer, an increase driven by the proliferation of targeted therapies in the area of thoracic oncology. The advent of precision medicine in oncology has raised new questions about how to adapt the evaluation and approval process to capitalize on the potential of these new technologies. IASLC Lung Cancer News spoke with Gideon Blumenthal, MD, from the FDA’s Office of Hematology and Oncology Products (OHOP) about these challenges, including the use of surrogate endpoints in lung cancer trials and the emergence of next-generation sequencing (NGS) in oncology.

Q: Last year, you and your colleagues published a meta-analysis of NSCLC trials in the Journal of Clinical Oncology1 that showed a strong association between overall response rate (ORR) and progression-free survival (PFS), but not between either of these surrogate endpoints and overall survival (OS). Are there ways to improve how surrogate endpoints are used in clinical trials?

A: That is a great question, and certainly something we ruminate over all the time.

While it is true that we did not observe associations on a trial level between ORR and OS or between PFS and OS, there are some caveats to those results. High rates of crossover might wash out the effect on OS, and if the target population is small, it may be hard to power a study to see a survival benefit. Also, patients with oncogeneaddicted malignancies such as EGFR or ALK can live a long time after progression, contributing to the difficulties of designing a study to detect a survival gain.

Particularly in trials of some immunotherapies, ORR and PFS do not seem to fully capture the clinical benefits of some of these agents. Are there new ways to measure responses to these treatments? That is an area in OHOP that we are definitely investigating. We are also talking to thought leaders in the lung cancer community because we know there are others in the academic community looking at this issue as well.

Q: NGS offers new opportunities to dramatically expand the genetic character-

ization of both patients and tumors. How do you think these technologies will affect the way new cancer therapies are tested and used in the clinic?

A: I have recently co-written an article in JAMA Oncology on this issue.2 I think

lung cancer doctors are at the forefront of using NGS both in terms of selecting patients for trials and in using information derived from NGS in the clinic because

there are at least 2 actionable mutations in lung cancer, EGFR and ALK, and in the near future there may be others. Using a single multiplex platform makes a lot of sense in lung cancer patients because tissue is scarce in the metastatic setting and we could potentially spare patients repeated biopsies.

From a drug development standpoint, the model of 1 companion diagnostic for a single drug may soon give way to a model using a single platform that has several companion diagnostic indications with several drugs tied to it.

That way, drug developers and device manufacturers don’t have to reinvent the wheel with every development program. It also makes a lot of sense from a research perspective because you can see many different genomic changes at the same time with a single test. There was a public workshop on February 25, 2016 to discuss some of these NGS-based oncology panels. We hope that there will be many platforms that can be used, but the key issue is standardizing these platforms so that the calls you get on one platform are the same as the calls you get from a different vendor.

Q: Are there any big developments on the horizon in the development of precision medicine for lung cancer treatment such as testing circulating tumor DNA (ctDNA), and if so, how will this be integrated into the approval process?

A: I think ctDNA is a very exciting emerging technology because it has a lot

of potential clinical applications: early detection, risk stratification of patients after surgical resection, monitoring patients, and even potentially down the road as a surrogate endpoint to discern drug activity. The FDA is in the early planning stages of a workshop on ctDNA in lung cancer this summer.

The other big development has been the emergence of immunotherapies in lung cancer. We approved our first 2 immunotherapies for the treatment of certain types of lung cancer in 2015, and there is a lot of interest in combining various immunotherapies, developing biomarkers to identify patients more likely to respond or not respond to an immunotherapy, and enhancing the immune response.

References 1. Blumenthal GM, Karuri SW, Zhang H, et al. Overall response rate, progression-free survival, and overall survival with targeted and standard therapies in advanced non-small-cell lung cancer: US Food and Drug Administration trial-level and patient-level analyses. J Clin Oncol.

2015;33(9):1008-1014.

2. Blumenthal GM, Mansfield E, Pazdur R. Next-Generation Sequencing in Oncology in the Era of Precision Medicine. JAMA Oncol. 2016;2(1):13-14.

corner

INTERVIEW WITH gideon blumenthal, MD /

Proceedings at the 16th Annual Meeting on Targeted Therapies for Lung Cancer.

to informally discuss their latest research and network with colleagues,” says Fred R. Hirsch, MD, PhD, IASLC Chief Executive Officer. “Many of the scientific presentations later made at larger meetings around the globe are first discussed at this event.”

“Coverage and summaries of scientific meetings around the globe and throughout the world are a core content area of IASLC Lung Cancer News,” said Dr. Corey J. Langer, Editor. “The Annual Meeting on Targeted Therapies for Lung Cancer is comprehensive; it provides an important platform leading to continued collaboration and scientific discovery so vital for the treatment of patients with lung cancer.” ✦

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IASLC Lung Cancer News / APRIL 2016

M eeting H I G H L I G H T S

Best of the 16th WCLC in Athens, Greece The International Association for the Study of Lung Cancer (IASLC) and the Oncology Unit of the 3rd Department of Medicine, Medical School of Athens, "Sotiria" Hospital, Greece organized and hosted the Best of the 16th World Conference of Lung Cancer (WCLC) in Athens, Greece, on January 14, 2016.

The conference was successful.

Almost 400 doctors attended. In addition, live streaming allowed further access both nationally and Europe-wide with 50 doctors from Athens, Greece, 140 European physicians from Hungary, Russia, Poland, and the United Kingdom attending the conference virtually through the Internet.

The meeting’s faculty was multinational and included Greek, British, French, Israeli, Spanish, Turkish, and American speakers. Each lecturer presented a medical topic from the 16th WCLC honed to his or her special area of medical interest.

The scientific program included thoracic oncology topics with high impact in our daily clinical/research practice such as prevention/tobacco control, screening/ early detection of lung cancer, biology,

pathology, and molecular testing. A separate session that focused on the treatment of localized NSCLC disease concluded the first day of the meeting. In addition, Ramon Rami-Porta, MD, chaired a round table on “New Staging System for NSCLC.” The second day of the meeting included updates from the 16th WCLC on the topics of screening for lung cancer, thoracic surgery, radiotherapy, medical oncology, nursing, tobacco control, supportive care and thoracic malignancies beyond NSCLC. The scientific audience was multidisciplinary in nature and included trainees, early career doctors, consultants, and experts from all the subspecialties involved in the management of lung cancer.

The meeting was an opportunity for our colleagues from Greece to interact with colleagues from neighboring countries, mainly the Balkans and the Middle East, and to participate at a highly scientific event that had content focused on the latest studies presented at the IASLC WCLC.✦

Professor Kostas Syrigos and Fred R. Hirsch, MD, PhD.

global research report

Afatinib Outperforms Gefitinib in Advanced Non-Small Cell Lung Cancer

By Erik J. MacLaren, PhD

The pan-ErbB inhibitor afatinib (Gilotrif) improves progression-free survival (PFS), time-to-treatment-failure (TTF) rate, and objective response rate (ORR) compared to the first-generation EGFR inhibitor gefitinib (Iressa) as a first-line treatment in patients with EGFR mutation-positive NSCLC, according to results presented at the ESMO Asia 2015 Congress in Singapore.1 Afatinib and gefitinib are both approved for first-line treatment of NSCLC with EGFR mutations based on phase 3 clinical trials that demonstrated their superiority to chemotherapy in that setting. In contrast to gefitinib, a first-generation EGFR tyrosine kinase inhibitor (TKI), afatinib irreversibly blocks members of the ErbB family of receptors, including EGFR, HER2, and ErbB4. In preclinical studies, afatinib has been shown to potently inhibit both wild type and mutated EGFRs, including those with the resistance mutation T790M. Because acquired resistance frequently develops in patients treated

with EGFR TKIs, and previous studies had suggested that afatinib could prolong responses and delay progression, Keunchil Park, MD, PhD, head of the Division of Hematology/Oncology at Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, and colleagues conducted a headto-head comparison of afatinib and gefitinib in previously untreated patients.

“

most common EGFR mutation was an exon 19 deletion, which was found in 57.5% of the afatinib group and 58.5% of the gefitinib group.

At the conference, Dr. Park highlighted the positive results for progression-free survival (PFS). “First-line afatinib treatment significantly reduced the risk of lung cancer progression by 27% versus gefitinib,” he said. “Interestingly,

First-line afatinib treatment significantly reduced the risk of lung cancer progression —Keunchil Park, MD, PhD by 27% versus gefitinib.

” A total of 319 patients were randomized to receive 40 mg daily afatinib (n = 160) or 250 mg daily gefitinib (n = 159). Baseline characteristics were similar in both treatment groups. Just over half of the participants were Asian (58.8% and 55.3%, respectively), and the

the improvement in PFS became more pronounced over time, with a significantly higher proportion of patients alive and progression-free at 18 months (27% vs 15%; P = 0.018) and 24 months (18% vs 8%; P = 0.018), showing a greater long-term benefit of using the irreversible

ErbB family blocker afatinib.”

In addition to the promising PFS results, response rates were also higher for patients in the afatinib arm (70%) than those receiving gefitinib (56%), and the median duration of response was 10.1 months for afatinib compared to 8.4 months for gefitinib. Discontinuation due to adverse events was 6.3% for both arms, indicating, from a practical standpoint, a comparable safety profile for both drugs.

“Based on these results, I would consider afatinib as the EGFR TKI of choice for the first-line treatment for patients with EGFR mutation-positive NSCLC,” noted Dr. Park. ✦ References 1. Park K, Tan E, Zhang L, et al. Afatinib (A) vs gefitinib (G) as first-line treatment for patients (pts) with advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutations: results of the global, randomized, open-label, Phase IIb trial LUX-Lung 7 (LL7). Paper presented at: 2015 ESMO Asia Congress; December 18-21, 2015; Singapore.

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IASLC Lung Cancer News / APRIL 2016

feature article

Update on Checkpoint Inhibitors in Lung Cancer

By Erik J. MacLaren, PhD

The growing number of checkpoint inhibitors currently being developed, without question, has ushered in a new era in clinical oncology, particularly in the treatment of thoracic malignancies.

These agents block various components of the immune checkpoint pathway, such as programmed cell death-1 (PD-1) receptor, which is expressed on the surface of immune cells, and its ligand PD-L1, which is frequently expressed on tumor cells and allows them to evade immune surveillance. By blocking checkpoint signaling, these drugs unleash the power of the patient’s own immune system against malignancies. Drugs targeting PD-1 have moved into the clinic in recent years for use in patients with melanoma, and in 2015, the FDA approved the first two immunotherapeutic agents for use in lung cancer.

The PD-1 inhibitor nivolumab (Opdivo) received approval in March 2015 for use in patients with advanced squamous non-small cell lung cancer (NSCLC) whose disease has progressed on platinum-based chemotherapy. In October 2015, approval was expanded to advanced non-squamous NSCLC as well. That month, the FDA approved another PD-1 antibody for the treatment of NSCLC, pembrolizumab (Keytruda).

Table 1. Summary of Phase 3 Trial Results for Nivolumab and Pembrolizumab in NSCLC. CheckMate 017 Histology

Squamous

Non-squamous

KEYNOTE-010 Squamous and Non-squamous; PD-L1 positive

Treatment Group

Nivolumab (n = 135)

Docetaxel (n= 37)

Nivolumab (n=292)

Docetaxel (n=290)

Pembrolizumab 2 mg/kg (n=345)

Pembrolizumab 10 mg/kg (n=346)

Docetaxel (n = 343)

Response Rate

20% P=0.008

9%

19% P=0.002

12%

18% P=0.0005

18% P=0.0002

9%

Median PFS* [95% CI]

3.5 months [2.1—4.9]

2.8 [2.1—3.5]

2.3 [2.2—3.3]

4.2 [3.5—4.9]

3.9

4.0

4.9

Median OS** [95% CI]

9.2 months [7.3—13.3]

6.0 [5.1—7.3]

12.2 [9.7—15.0]

9.4 [8.1—10.7]

10.4 [9.4—11.9]

12.7 [10.0—17.3]

8.5 [7.5—9.8]

Hazard ratio for death

0.59 P<0.001

0.71 P=0.0008

0.61 P<0.0001

0.73 P=0.002

* Progression-free survival **Overall Survival

marker. Data from the nivolumab trials showed that PD-L1 expression levels were positively correlated with treatment benefits in non-squamous NSCLC with respect to response rates and OS, but not in squamous NSCLC. Consequently, work continues to better define the optimal role for PD-L1 expression in patient selection.

The success of anti-PD-1 drugs in NSCLC has also led to a flurry of interest in other checkpoint inhibitors. The results of the BIRCH4 and POPLAR 5 trials of another PD-L1 antibody,

The success of these anti-PD-1 drugs in NSCLC has also led to a flurry of interest in other checkpoint inhibitors.

Nivolumab was also approved last year by the European Medicines Agency for second-line treatment of squamous NSCLC. Results from two phase 3 trials, CheckMate 0171 and CheckMate 057,2 demonstrated that second-line nivolumab prolonged overall survival (OS) compared to docetaxel in an unselected population of patients with squamous and non-squamous NSCLC, respectively; and the phase 3 KEYSTONE-0103 trial showed that pembrolizumab increased OS compared to docetaxel in patients with PD-L1 positive NSCLC (Table 1).

Importantly, not only did these studies establish that nivolumab and pembrolizumab prolonged patient survival, but they were also associated with far fewer adverse events and improved quality of life compared to docetaxel.

These positive results in both histologically determined, otherwise-unselected populations have raised questions about the predictive power of PD-L1 as a bio-

CheckMate 057

atezolizumab, were presented at the European Cancer Congress 2015 in Vienna, Austria. Data from these trials showed that atezolizumab had activity in patients with refractory lung cancer regardless of the number of prior treatments, and that it increased OS in unselected patients with NSCLC compared to single-agent docetaxel. PD-L1 expression levels, both in the cancer cells and in the immune microenvironment, were again positively correlated with treatment benefit.

Studies are also being conducted in which monoclonal antibodies targeting PD-1 or PD-L1 are combined with inhibitors of another immune checkpoint receptor found on T cells, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Although combinations of checkpoint inhibitors are predicted to have greater anti-tumor activity compared to either agent alone, concerns have been raised that patients will be unable to

tolerate the overlapping toxicity profiles of these drugs.

Results from a phase 1b trial of the combination of the PD-L1 antibody durvalumab (MEDI 4736) and the CTLA-4 antibody tremelimumab in patients with advanced NSCLC were presented at the European Society for Medical Oncology Asia Congress in Singapore in December 2015, and published this year in The Lancet Oncology.6 The authors identified a dose combination with a manageable safety profile and a response rate of 23%. In contrast to the results from many single-agent PD-1 inhibitor trials, PD-L1 status had no effect on the observed response rates. These results are being followed up with several phase 3 trials, NCT02352948, NCT02453282, and NCT02542293, to examine the efficacy of this combination as first-line therapy for advanced NSCLC in a larger population.

Considering these and other successes for checkpoint inhibitors in thoracic cancer, 2015 signals only the beginning of a gradual move away from chemotherapy to agents that are more effective and safer for the treatment of advanced lung cancer. Clinicians and patients alike have reasons to follow the results of these trials with great interest. ✦ References 1. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015;373(2):123-135.

2. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015;373(17):1627-1639.

3. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial.

Lancet. 2015.

4. Besse B, Johnson M, Jänne PA, et al. Phase II, single-arm trial (BIRCH) of atezolizumab as first-

line or subsequent therapy for locally advanced or metastatic PD-L1-selected non-small cell lung cancer (NSCLC). Paper presented at: European Cancer Congress2015; Vienna, Austria.

5. Vansteenkiste J, Fehrenbacher L, Spira AI, et al.

Atezolizumab monotherapy vs docetaxel in 2L/3L non-small cell lung cancer: Primary analyses for efficacy, safety and predictive biomarkers from a randomized phase II study (POPLAR). Paper presented at: European Cancer Congress2015; Vienna, Austria.

6. Antonia S, Goldberg SB, Balmanoukian A, et al.

Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. Lancet Oncol. 2016.

6th ELCC from page 1 clinician attendees who treat these cancers. This year’s meeting will highlight several themes. These include advances in immunotherapy, stereotactic radiation therapy, the treatment of molecularly defined non-small cell lung cancer, cancer screening, and minimally invasive local treatments. The new World Health Organization classification of lung tumors will also be featured, including its impact on patient care, from both the surgeon’s and pathologist’s viewpoint. The new IASLC staging system will also be discussed.

More than 1,600 international clinicians are expected to attend this year’s meeting, and throughout the conference, attendees can share updates from the meeting on social media using the dedicated #ELCC16 hashtag. The meeting will also feature eight industry satellite symposia and a wide range of commercial exhibitors, and will provide excellent opportunities for networking.

IASLC Lung Cancer News, this new professional tabloid publication targeted to thoracic cancer specialists, will also be launching at this meeting; conference delegates are encouraged to stop by and see us at the IASLC booth. ✦

IASLC Lung Cancer News / APRIL 2016

By Erik J. MacLaren, PhD

In late 2015, the US National Cancer Institute (NCI) Thoracic Malignancy Steering Committee (TMSC) published its strategic priorities for the coming years.

These include: (1) innovative clinical trials to facilitate the development of immunotherapies and targeted therapies; (2) rapid testing of new agents to treat small cell lung cancer (SCLC); (3) exploration of neoadjuvant therapy for resectable non-small cell lung cancer (NSCLC); and (4) determining the optimal roles for new radiation approaches such as stereotactic body radiation therapy (SBRT).1 IASLC Lung Cancer News spoke with Shakun Malik, MD, Head, Thoracic and Head & Neck Cancer Therapeutics, from the NCI Cancer Therapy Evaluation Program (CTEP), and a member of the TMSC, about these goals and the future of thoracic cancer trials under the aegis of the NCI.

A: The concept of using master protocols came about in 2012, during an

Q: What is your current vision for the NCI Thoracic Oncology Program?

last year, we have added a combination immunotherapy arm to Lung-MAP for patients with advanced squamous cell lung cancer in the second-line clinical setting. For ALCHEMIST, we have approved an additional treatment trial that will test an immunotherapeutic agent, nivolumab, in patients with resected early-stage lung cancer after completion of standard therapy.

In addition to activating a study of afatinib, (a second-generation EGFR small molecule inhibitor) with or without cetuximab (an EGFR antibody) in patients with EGFR mutation in their tumors, a trial of immunotherapy with or without Stereotactic Body Radiation Therapy (SBRT) in limited metastatic setting has also just been approved. Several phase I and small phase II trials testing other new investigational treatments have also been approved by CTEP’s early-phase Experimental Therapeutics Clinical Trials Network (ETCTN).

A: My vision is to enhance our preclinical and translational work in a way that

ultimately helps us design clinical trials leading to new innovative treatments to improve the care and overall survival of patients with lung cancer. There are many molecular targets that have been discovered recently; however, we need to get a better understanding of how they drive tumor growth. We now have a proliferation of immunotherapies in oncology, but we still do not know which patients will benefit the most from these new agents. In clinical trials data, there is a tail end of the curve where some patients have benefited the most. We need to focus our efforts and learn more about the tumor characteristics of these patients.

With the focus on expanding Precision Medicine clinical trials, there is an opportunity for all of us (NCI, pharma industry, FDA, and private sectors) to work in unison to accelerate clinical research leading towards improvements in treatment.

Q: How do you see the NCI functioning in the context of both industry and the National Clinical Trials Network (NCTN), which was formerly known as the Cooperative Group Program?

A: I do not think that one can function without the other in this era of precision

medicine clinical trials and drug development. There has to be cooperation among all stakeholders, particularly industry, the NCTN, the NCI, and the FDA. With the discovery of multiple molecular targets that drive cancer cell growth, a common cancer like lung cancer is now recognized as having multiple molecular subtypes of the disease. Collaborations among all stakeholders can accelerate progress on new treatments.

Q: Please describe the concept behind master protocols like S1400. Where else in thoracic oncology do you think this can be implemented?

NCI and FDA workshop that led to the development of the Lung-MAP and ALCHEMIST trials.2 The goal was to provide a centralized screening approach in one master protocol in order to match patients to sub-studies testing investigational new treatments based on the molecular characterization of their tumors instead of mounting multiple, separate clinical trials. It takes an extensive infrastructure and resources to conduct master protocols.

Of course, there has been a bit of a learning process with these new master protocol studies, but I think both of the trials are doing very well. This strategy can be implemented in other areas as well when there is a need for a centralized screening approach to match patients to studies based on the molecular characteristics of their tumors.

Q: Can you tell us what studies have been approved by CTEP recently?

A: There are a number of studies that we are working on currently. Over the

Q: What other issues should be addressed by the NCI and the NCTN? A: The NCTN is intended to encourage a consistently excellent clinical trials

program executed by an integrated Network of Groups conducting trials across a broad range of diseases and diverse patient populations. The challenge is to continue to work together to design and conduct clinically meaningful trials and to use the resources of the entire network to ensure timely completion of the studies in order to accelerate progress in cancer treatment.

References 1. Thoracic Malignancy Steering Committee. 2015 Strategic Priorities: Thoracic Malignancy Steering Committee (TMSC). http://www.cancer.gov/about-nci/organization/ccct/steeringcommittees/2015-TMSC-StrategicPriorities: National Cancer Institute; November 2015.

2. Malik SM, Pazdur R, Abrams JS, et al. Consensus report of a joint NCI thoracic malignancies steering committee: FDA workshop on strategies for integrating biomarkers into clinical development of new therapies for lung cancer leading to the inception of “master protocols” in lung cancer. J Thorac Oncol. 2014;9(10):1443-1448.

IASLC MeMberShIp benefItS InCLude:

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Collaboration with a global team of thoracic oncology experts and leaders

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Member access to Journal of Thoracic Oncology, the premier journal in lung cancer, as well as the latest classification and staging publications

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INTERVIEW WITH SHAKUN MALIK, MD /

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IASLC Lung Cancer News / APRIL 2016

lung cancer screening

Implementation of Lung Cancer CT Screening: A Global Dream or a Real Possibility?

By Professor John K. Field MA, PhD, BDS, FRCPath

The advent of lung cancer computed tomography (CT) screening was initiated by the Early Lung Cancer Action Project (ELCAP) group in 19991 with their seminal publication in Lancet. This focused attention on the possibility of introducing CT screening as an early detection strategy, resulting in the funding of the National Lung Screening Trial (NLST) >53,000 persons trial in 2002, which by all accounts has been the largest randomized controlled lung cancer trial ever undertaken. The NLST trial demonstrated a 20% relative reduction in lung cancer mortality in the CT-screened arm compared to the chest X-ray arm.2,3 IASLC held a special CT screening workshop just days after this publication at World Conference on Lung Cancer (WCLC) 2011, from which the 75-member working group published their set of recommendations and posed specific outstanding questions.4 This is the good news; however, it has taken some time for CT screening to be implemented in the US, and only after recommendations from the US Preventive Services Task Force on CT screening and Medicare’s agreement to fund screening, within specific criteria.5 In Europe, a number of smaller trials have been undertaken in Italy, Denmark, Germany, and more recently in the UK; the largest of the European trials is the NELSON, which was undertaken in the Netherlands and Belgium (RCT CT vs no scan).6 We eagerly await the outcome of the NELSON trial in 2016/17, which will potentially herald the implementation of CT screening in Europe. There is also considerable experience in lung cancer CT screening trials in Japan, and more recently in China and Australia.

The question may be asked why has CT screening not been readily implemented outside the US? Clearly, the US has an insurance-based health care system, which is different from Europe and many other parts of the world. However, the focus is not only on a mortality reduction but also on cost-effectiveness. The NLST cost-effectiveness worked out to $81,000 (CI $52,000- $186,000) per quality adjusted life year (QALY), but most likely reflects the more costly health care system in the States.7 Recently, the UK Lung Cancer Screening (UKLS) modelled the baseline screening cost-effectiveness at £8,466 per QALY, ($13,071 per QALY gained (CI $8,556-$19,405).8 Thus, even allowing for the UKLS modelling being based on the baseline CT scans, it falls

comfortably within the acceptable UK National Institute for Health and Care Excellence (NICE) guidelines (£20,000£30,000/QALY).

One of the outcomes of the IASLC CT screening workshop in 2011 was setting up the IASLC Strategic Screening Advisory Committee (SSAC), which has hosted 1-day workshops at WCLC 2013 in Australia and WCLC 2015 in Denver.

These SSAC workshops have provided an opportunity to collegially involve global experts in discussing the outstanding

questions concerning the practical issue of implementation, radiologic protocols, management of indeterminate nodules using volumetric analysis and volume doubling time (Figure 1), as well as considering the screening intervals and the patients’ lifetime involvement in future CT screening programs as outlined in a series of questions in Lancet in 2013 (Figure 2).9 We now need to focus on identifying the “hard-to-reach” communities and use the risk prediction models that have been demonstrated

to successfully guide the selection of high-risk individuals for lung cancer CT screening programs. Looking to the future, the development and incorporation of molecular-genetic risk biomarkers into clinical-epidemiologic risk models will be a major research focus in the coming years. Currently, there is little discussion in the literature as to how the implementation of future CT screening programs will affect health care service delivery and how we will develop continued on page 13

A B

D C

Figure 1. Examples of various sizes of nodules visually detected and characterized volumetrically using Siemens LungCare software (from individuals enrolled in the UKLS pilot study). A) Inconspicuous small nodule not fulfilling the volumetric size criterion of a UKLS Category 1 nodule (>15mm3 volume) – this 9.59mm3 nodule would not be followed up in the UKLS care pathway. B) Category 2 nodule (15-49 mm3) – a follow-up CT would be performed at 1 year. C) Category 3 nodule (50-500 mm3) – a follow-up CT would be performed at 3 months. D) Category 4 nodule (>500 mm3) – such a nodule would mandate referral for multidisciplinary team assessment. Reprinted with permission from: CT screening for lung cancer: countdown to implementation. Field JK, Hansell DM, Duffy SW, Baldwin DR. Lancet Oncol. 2013 Dec;14(13):e591-600.

High-risk stratification model

Age >65-75 years

LDCT size and volume protocol

FNA, EBUS other?

Surgery: VATS? Stereotactic radiotherapy

Annual or biennial screen?

Screen for defined period?

Costeffectiveness

Who?

When?

How?

Workup?

Treatment?

Repeat CT scan?

Years?

How much?

Figure 2. Decisions for implementation of CT screening. LDCT=low-dose CT. FNA=fine-needle aspiration. EBUS=endobronchial ultrasound.

VATS=video-assisted thoracoscopic surgery. Reprinted with permission from: Prospects for population screening and diagnosis of lung cancer.

Field JK, Oudkerk M, Pedersen JH, Duffy SW. Lancet. 2013 Aug 24;382(9893):732-41.

International Association for the Study of Lung Cancer

Lung Cancer Foundation of America and The International Association for the Study of Lung Cancer are proud to announce a

Request for Application for:

• 2 LUNG CANCER RESEARCH GRANTS • $200,000 EACH GRANT • OVER 2 YEARS

For more information, please visit:

www.LCFAmerica.org/Lung-Cancer-Research-Grants-2016.html

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IASLC Lung Cancer News / APRIL 2016

S mo k ing C essation and T obacco C ontrol

Clinicians and Tobacco—What Can We Really Do?

By Emily Stone, MBBS, MMed, FRACP, and Graham Warren, MD, PhD

also been shown in patients treated with stereotactic body radiotherapy.9 Several studies highlighted in the 2014 SGR delineate the benefits of smoking cessation.1 The National Comprehensive Cancer Network (NCCN) has recently developed structured guidelines for smoking cessation in all cancer patients.10 Smoking cessation in patients with known or suspected lung cancer is an essential part of lung cancer treatment.

As clinicians, we often discuss smoking cessation with our patients, but we may less commonly consider the effect of population-based strategies. Tobacco control strategies have dramatically reduced smoking rates and improved health outcomes in countries that have implemented them. Clinicians can act as leaders to assist in local, regional, and

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• Smoking cessation reduces the risk of lung cancer and of overall cause mortality in smokers, with up to 10 years of life saved in young smokers who quit • Smoking cessation in lung cancer patients improves outcomes, including after treatment • Smoking cessation may be enhanced by lung cancer screening • Tobacco control strategies are highly successful in reducing smoking rates and improving cessation wherever they are effectively applied • The tobacco industry actively opposes tobacco control, interfering with government policy and pursuing new markets in vulnerable populations

1964 Surgeon General's report on smoking and health Broadcast ad ban Synar Amendment enacted

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Nicotine medications available over-the-counter

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Master Settlement Agreement

Federal cigarette tax doubles

Fairness Doctrine messages on broadcast media US entry into WWI

1986 Surgeon General’s report on FDA secondhand smoke proposed rule Cigarette price drop

Federal $0.62 2006 Surgeon General’s tax increase report on secondhand smoke (update)

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national tobacco control efforts. The cornerstone of international tobacco control is the WHO Framework Convention on Tobacco Control and its MPOWER measures. The most effective strategies focus on tobacco taxation and cigarette price, smoking bans, and advertising bans including plain packaging. The many examples of such strategies are outside the scope of this brief article, but the accompanying figures demonstrate their effects on tobacco consumption in the US (Figure 1), in South Africa (Figure 2), and on adolescent smoking rates in Australia (Figure 3). Unfortunately, adverse governmental influence can severely impair tobacco control efforts. In China, the tobacco industry is a state-owned monopoly regulated (and promoted) at the highest government level, with power

Figure 1. Adults aged ≥18 years per capita cigarette consumption and major smoking and health events, United States, 1900–2012. Reprinted from U.S. Department of Health and Human Services. The Health Consequences of Smoking: 50 Years of Progress. A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014.

Smoking Prevalence (%)

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Tobacco control is set to become one of the most clinically effective and rapidly developing areas in lung cancer medicine. Since the original publication of the US Surgeon General’s Report (SGR) on Smoking and Health in 1964, the 2014 SGR report details the most current advances and observations: 1) tobacco use causes a wide spectrum of diseases, 2) tobacco cessation at any age results in significant health benefits, 3) smoking by cancer patients and survivors causes adverse cancer treatment outcomes, and 4) continued tobacco consumption will cause substantial financial and healthrelated economic costs worldwide.1 To prevent these effects, tobacco control measures must reduce smoking rates.

The link between smoking and lung cancer cannot be refuted. Starting with large pivotal studies that linked higher rates of lung cancer in people with higher rates of smoking,2,3 data are now conclusive that smoking causes 80%-90% of all lung cancer. The concomitant rise in tobacco consumption has turned lung cancer from a rare disease with several hundred cases annually in 1900 to several hundred thousand cases currently.

Patterns have emerged worldwide. In high-income countries, the lung cancer epidemic is showing the effects of strong tobacco control, with peak lung-cancer incidence rates in men occurring around 1980,4 a couple of decades after the first US Surgeon General’s Report. Between 1964 and 1980, these countries witnessed the institution of multiple tobacco control measures and a subsequent decline in smoking in men. In many countries, we have yet to see stabilization or decline in lung cancer rates in women. Product design, including the introduction of filtered cigarettes and menthol over the past 50 years, has not reduced the harms of tobacco consumption and, in fact, has resulted in a more severe addiction.5 The benefits of smoking cessation are particularly relevant to lung cancer screening and cancer treatment. The National Lung Screening Trial study originally showed a 20% reduction in mortality for patients who received CT screening.6 Impressively, follow-up analysis of the same trial demonstrated substantial reductions in mortality for patients who quit smoking, benefits that matched those of CT screening for patients who quit smoking for 7 years.7 Smoking cessation reduced mortality by 45% in a cohort of lung cancer patients who received phonebased cessation support.8 The benefits of smoking cessation after diagnosis have

over the introduction of tobacco control measures due to its structural integration into the government bodies that oversee both tobacco industry growth and tobacco control. In Poland, recent efforts by tobacco industry representatives have influenced the content of tobacco control legislation. In the Netherlands, weakening of tobacco control legislation over recent years has raised concern about links between senior government members and the tobacco industry. The global tobacco industry is a critical driver of the current and future lung cancer epidemic. Opposing this are groups in all countries working actively to curb the adverse effects of tobacco. When pro-

IASLC Lung Cancer News / APRIL 2016

moting tobacco cessation in cancer care, clinicians should consider the tobacco control context in which they work and promote tobacco control efforts that benefit their patients and their own society. ✦ 1. Alberg AJ, Shopland DR, Cummings KM. The 2014 Surgeon General’s Report: Commemorating the 50th Anniversary of the 1964 Report of the Advisory Committee to the US Surgeon General and Updating the Evidence on the Health Consequences of Cigarette Smoking.

Am J Epidemiol. 2014; 179:403–12.

2. Wynder EL, Graham EA. Tobacco smoking as a possible etiologic factor in bronchiogenic carcinoma; a study of 684 proved cases. J Am Med Assoc. 1950;143:329–36.

3. Doll R, Hill AB. Smoking and carcinoma of the lung; preliminary report. Br Med J. 1950; 2:739–48.

4. Islami F, Torre LA, Jemal A. Global trends of lung cancer mortality and smoking prevalence. Transl Lung Cancer Res. 2015; 4:327–38.

5. Thun MJ, Carter BD, Feskanich D, et al. 50-Year Trends in Smoking-Related Mortality in the United States. N Engl J Med. 2013; 368:351–64.

6. National Lung Screening Trial Research Team, Church TR, Black WC, et al. Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med. 2013; 368:1980–91.

7. Tanner NT, Kanodra NM, Gebregziabher M, et al. The Association Between Smoking Abstinence and Mortality in the National Lung Screening Trial. Am J Respir Crit Care Med. 2015;

Percentage of Adolescents Who are Current Smokers

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2007 Smoke-free enclosed public places in pubs, clubs, nightclubs and casinos (except private gaming areas) 2004 1997 2008 NSW announced smoking Launch of National Increased penalties for selling tobacco and in indoor areas or licensed Tobacco Campaign nontobacco smoking products to minors premises would be phased 2009 1999 out by July 2007 Ban on smoking in cars with children Changes to 2005 tobacco excise 2010 Commencement Point-of-sale reforms, including 2000 of antismoking tobacco display ban Smoking banned inside campaigns in NSW restaurants and cafes 25% increase in tobacco excise 2006 Health warnings on 2012 tobacco packaging Smoke-Free Environment Act 2000 prohibiting smoking ACCC National in certain public outdoor places Tobacco Campaign Plain packaging introduced

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Figure 3. Factors affecting declines in adolescents smoking in Australia, 1996–2014. Reprinted from Public Health Res Pract. 2016;26(1):e2611605.

Available from: http://www.atsjournals.org/doi/ abs/10.1164/rccm.201507-1420OC. 8. Dobson Amato KA, Hyland A, Reed R, et al.

Tobacco Cessation May Improve Lung Cancer Patient Survival. JTO. 2015; 10:1014–9.

9. Roach MC, Rehman S, DeWees TA, Abraham CD, Bradley JD, Robinson CG. It’s never too late: Smoking cessation after stereotactic body radiation therapy for non-small cell lung carcinoma improves overall survival. Pract Radiat Oncol.

2016; 6:12-8.

10. NCCN Clinical Practice Guidelines in Oncology, Smoking Cessation. 2015. Available from: http:// www.nccn.org/professionals/physician_gls/pdf/ smoking.pdf.

From the Editor from page 1

• Managing Toxicities and Patient Expectations • Survivorship Perspectives • Lung Cancer in the Media • Names in the News Our intention is to accomplish the following: • Signal our evolving understanding of tobacco control and lung cancer screening • Underscore current debates and controversies in the interdisciplinary management of patients with lung cancer • Summarize recent advances and innovations in genomic sequencing and target therapies • Expand our working knowledge of immunotherapeutics in thoracic malignancy

11

• Describe reported advances in basic and translational sciences by lung cancer researchers • Highlight the activities and impact of lung cancer leaders and advocates in the care of patients with lung cancer On behalf of my Associate Editors and Deborah Whippen, Managing Editor and Publisher, I welcome your attention, your input, and suggestions. ✦ Corey J. Langer, MD, FACP

Editor, IASLC Lung Cancer News Director of Thoracic Oncology Abramson Cancer Center Professor of Medicine Perelman School of Medicine University of Pennsylvania

IASLC President Welcome from page 1

Up until a few years ago, we had a one-size-fits-all approach to the management of lung cancer. Tumor genomics and molecular therapeutics have recently spurred a paradigm shift in our treatment standards for lung cancer. We now know that every lung cancer and every patient is unique, and that defining the presence or absence of key biomarkers in each patient is crucial for matching that patient to the most appropriate treatments. Today, patients with lung cancer and related malignancies can be offered hope for more effective, less toxic personalized therapies. Science is directly affecting patient care, and scientists who take care of patients are discovering new science.

In this and future issues, contributors will describe new insights, opportunities, and challenges of potential importance for researchers and health care providers relevant to our patients with thoracic cancers. I welcome the readership to this important publication.✦

Help Others Succeed foundation The IaSlC Foundation supports the education of fellows and young investigators who will be the next generation of lung cancer physicians and scientists.

learn mOre at www.iaslc.org/foundation

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IASLC Lung Cancer News / APRIL 2016

S ur v i v orship

Lung Cancer Survivor Wins Trip to US NFL 2016 Pro Bowl

By Nicola M. Parry, DVM

Lung cancer survivor Kathy Weber is an ardent ambassador for the International Association for the Study of Lung Cancer (IASLC). “My involvement with the IASLC comes from attending the World Conference on Lung Cancer (WCLC), as

2.5 miles each day: “My son was a huge helper, he walked with me every day— encouraging me to go to the next fence post, or next gate, each time we walked.

He would say, ‘You can do it, Mom, just a little further.’”

Having competed in figure bodybuilding, she was very aware of her body, and knew something was wrong when she developed muscle atrophy and nerve pain in her right shoulder and could no longer do a push-up. well as a survivors’ get-together at their main office,” she explained, emphasizing how impressed she is with the IASLC— the only global organization that unites experts across different disciplines who are involved in treating lung cancer, with more than 5,000 members in over 100 countries.

Kathy—an otherwise healthy, young, never-smoker—was diagnosed with stage 1A lung cancer in the spring of 2014.

Having competed in figure bodybuilding, she was very aware of her body, and knew something was wrong when she developed muscle atrophy and nerve pain in her right shoulder and could no longer do a push-up. Her physical therapist, John Graham, PT, was also concerned that these issues were not just related to a muscle problem, but could signify a serious underlying problem such as a tumor in her right upper chest. “Without question, my PT John was someone I trusted,” said Kathy. “So, when he agreed that something was wrong, there was no doubt I was going to pursue it.” Indeed, after consulting her physician about the problem, a diagnostic workup was pursued, and x-rays and CT scans of Kathy’s chest ultimately revealed the presence of a small nodule, which was later removed at surgery and diagnosed as stage IA lung adenocarcinoma.

Kathy then underwent a partial lobectomy, and she credits much of her remarkable recovery to the expertise of her University of Colorado surgeon, Michael Weyant, MD. “I had a videoassisted thoracoscopic surgery procedure,” she said, adding that, “with a surgery this big, what you want to hear when it is over is ‘there were no complications.’”

She recognizes that her active, healthy lifestyle also contributed to her speedy recovery. “I was told the best thing for me was to walk,” she said. Two weeks after her surgery, Kathy said she was walking

In her continued support of the IASLC, Kathy recently raised more than $10,000 to benefit the IASLC Foundation

Kathy Weber and family at US 2016 Pro Bowl.

Kathy Weber (R) and her aunt Christie Malnati (L), at a bodybuilding competition.

Kathy Weber post-op day 1.

and the Chris Draft Family Foundation, as the first runner-up in Team Draft’s 2016 Lung Cancer Survivors’ Super Bowl Challenge. Team Draft was founded by former US National Football League (NFL) player Chris Draft and his late wife, Keasha, who died at the age of 38 after a year-long struggle with stage IV lung cancer. The Super Bowl Challenge recruits lung cancer survivors in a friendly competition to raise both awareness and research funding for lung cancer—and the top 3 fundraisers enjoy trips to the NFL Super Bowl championship game, the NFL Pro Bowl, and the Taste of the NFL. Achieving second place in the fundraising challenge earned Kathy and her family a trip to this year’s NFL Pro Bowl in Hawaii on January 31st.

Kathy found out about Team Draft's Challenge from her aunt, also a lung cancer survivor, who had met Chris Draft at the 2015 WCLC in Denver, US. After learning about Keasha’s story and Chris Draft’s commitment to changing the face of lung cancer, Kathy knew she had to get involved. “Initially, after my diagnosis and surgery 18 months ago, I really didn't want to talk about lung cancer. I just wanted to get on with my life and kind of forget about the whole thing. I think they call that denial,” she said.

Although Kathy and her family were excited to go onto the field during the third quarter of this year’s Pro Bowl

game, she particularly enjoyed attending Pro Bowl practice. “Meeting the players and sharing my story was quite the experience,” she said. Another highlight was getting to know Chris Draft, his dad Tony, Keith Singer (videographer/photographer), and Billy Nash (Board Member for the Chris Draft Family Foundation).

“To be able to share this experience with my family was truly a blessing,” she said.

“The memories we made will be cherished forever.” During their trip, Kathy and her family also hiked to Likeke Falls, visited the Polynesian Cultural Center and Pearl Harbor, and enjoyed amazing shrimp scampi at Giovanni's Shrimp Truck.

Today, Kathy is doing extremely well.

She works out in the gym 3 or 4 days each week, and stressed that “being fast is not my goal, but being strong is”. Her next goal is to compete in a figure bodybuilding competition in the summer of 2017, just before she turns 50 years old. “I am currently training hard to put back on some muscle mass that I lost following surgery,” she said.

While half of the money Kathy raised will benefit Team Draft, the other half will go to the IASLC Foundation. “My goal is to continue to be an ambassador for the IASLC, raising lung cancer awareness and funding, and also supporting their research commitment for lung cancer patients like me who are young nonsmokers,” she concluded. ✦

IASLC Lung Cancer News / APRIL 2016 perspecti v e

Lung Cancer CT Screening from page 6

When Breath Becomes Air by Paul Kalanithi, MD

Memoir Resonates with Oncologists and Patients with Lung Cancer

By Lori Alexander, MTPW, ELS, MWC

How does a person with stage IV lung cancer live a meaningful life? That’s the question Paul Kalanithi explores in When Breath Becomes Air, the number 1 book on the New York Times Best Sellers list.

Kalanithi’s moving and honest reflection of his life as he transforms from physician to patient resonates with both oncologists and patients alike.

Kalanithi is a brilliant neurosurgical resident and only 36 years old when stage IV lung cancer is diagnosed, a diagnosis

live with uncertainty is one of our great challenges.”

In justifying his need for knowing the prognosis, Kalanithi writes, “The way forward would seem obvious, if only I knew how many months or years I had left. Tell me three months, I’d spend time with family. Tell me one year, I’d write a book. Give me ten years, I’d get back to treating diseases. The truth that you live one day at a time didn’t help: What was I supposed to do with that day?” In

gifts in the days remaining to me,” says Janet Freeman-Daily, now a lung cancer advocate and creator of the website, Gray Connections: Perspectives on Lung Cancer, Brain Science, and Other Stuff.

“Facing the very real possibility of death in the near term changes one’s perspective on life,” adds Freeman-Daily. “The

“ The way forward would seem obvious, if only I knew how many months or years I had left. Tell me three months, I’d spend time with family. Tell me one year, I’d write a book. Give me ten years, I’d get back to treating diseases.”

Credit: Norbert Von Der Groeben/Stanford Health Care

that he notes is given to only 0.0012% of people his age. But statistics have a different meaning for him now that he has become one, he writes. Once so sure of his career plan—20 years as a surgeonscientist and 20 years as a writer—he now wrestles with how to live out the rest of his days, especially given the uncertainty of how many days he actually has. He craves a specific prognosis, but his oncologist persists in not giving him one, instead repeatedly telling him, “You have to figure out what’s most important to you.” Is this the best approach?

“The statistics can never say how long an individual will survive. To give a limit on survival can mean taking away what an individual can be or do, and it can be wrong. Patients must find their own truth and meaning, and all doctors can do is to help frame that,” says Tracey Evans, MD, Associate Professor of Clinical Medicine, University of Pennsylvania.

Heather Wakelee, MD, Associate Professor of Medicine, Stanford University Medical Center, agrees. “It would be so much easier if we could tell people how much time they have, but we can’t, and helping people learn to

13

the end, Kalanithi goes back to his surgical residency, valiantly working to fulfill the requirements for graduation from his residency. And he and his wife Lucy decide to have the child they have always wanted.

“Is it better to overestimate, underestimate, or leave it open?” asks Dr. Evans. “It was clear Paul knew the statistics, yet the information provided by his oncologist still carried so much weight. I find this so incredibly humbling.”

Kalanithi’s struggles with a cancer diagnosis go beyond trying to identify his values. “The curse of cancer created a strange and strained existence, challenging me to be neither blind to, nor bound by, death’s approach,” he writes. “Even when the cancer was in retreat, it cast long shadows.”

Living in the shadow of a cancer diagnosis raises unanswerable questions for patients. “After my third-line treatment, when I achieved no evidence of disease (but unsure of how long it might last), I found myself wondering why I found effective treatment when so many others died. It made me question why I was here and how I could make the best use of my

Western world is obsessed with denying death as long as possible, yet the reality is that we will all die. Lung cancer forces one to confront that fact and accept that one’s time on earth is limited. It’s oddly freeing, enabling me to live in the joy of the moment and cherish whatever time I’ve been given. Yet, I sometimes feel regret for the things cancer and its treatment have taken from me.”

Physicians feel this regret as well. “I treat patients with cancer every day, and I am acutely aware of what cancer steals from the individual with the illness and their loved ones,” says Dr. Evans. “Paul’s writing makes that all the more apparent. No one is left untouched by cancer because…amazing individuals like Paul are taken from us. He would have contributed so much as a neurosurgeon, a physician, and a writer. All we have to offer did not allow Paul to live, to give us years as a practicing physician or loving father. However, I then realize that even the seemingly small accomplishments matter. The targeted treatment Paul received did not give him decades, but it gave him time to become a father and to write this book.”✦

accreditation systems for the next generation of radiologists involved in CT screening programs.

In this inaugural issue of IASLC Lung Cancer News, an overview of the current status of CT screening has been provided. Future issues of IASLC Lung Cancer News will focus on specific CT screening questions, which still need to be resolved, to continuously improve lung cancer early detection. The IASLC SSAC Workshops and meetings will take the lead on behalf of the Association to move this forward.✦ References

1. Henschke CI, McCauley DI, Yankelevitz DF, et al. Early Lung Cancer Action Project: Overall design and findings from baseline screening.

Lancet. 1999; 354: 99-105.

2. Aberle DR, Berg CD, Black WC, et al. The National Lung Screening Trial: Overview and study design. Radiology. 2011; 258:243-253.

3. National Lung Screening Trial Research Team, Aberle DR, Adams AM, et al. Reduced lungcancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011; 365:395-409.

4. Field JK, Smith RA, Aberle DR, et al.

International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 Report. J Thorac Oncol. 2012;7: 10-19.

5. de Koning HJ, Meza R, Plevritis SK, et al.

Benefits and harms of computed tomography lung cancer screening strategies: A comparative modeling study for the U.S. Preventive Services Task Force. Ann Intern Med. 2014; 160: 311320.

6. van Klaveren RJ, Oudkerk M, Prokop M, et al. Management of lung nodules detected by volume CT scanning. N Engl J Med. 2009; 361: 2221-2229.

7. Black WC, Gareen IF, Soneji SS, et al, National Lung Screening Trial Research T. Costeffectiveness of CT screening in the National Lung Screening Trial. N Engl J Med. 2014; 371:1793-1802.

8. Field JK, Duffy SW, Baldwin DR, et al. UK Lung Cancer RCT Pilot Screening Trial: Baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening. Thorax. 2016; 71: 161-170.

9. Field JK, Oudkerk M, Pedersen JH, Duffy SW. Prospects for population screening and diagnosis of lung cancer. Lancet. 2013; 382:732-741.

For information on placing advertisements, please contact Kevin Dunn at kdunn@cunnasso.com

14

IASLC Lung Cancer News / APRIL 2016

patient C are

Nurses Treating Lung Cancer, IASLC and Beyond

By Beth Eaby-Sandy, MSN, CRNP, OCN

As a nurse practitioner in an academic center in the US, I work in a thoracic medical oncology practice; however, in the US, it is uncommon for nurses or other advanced practice providers to specialize in one cancer disease site.

According to the NCI website, 85% of oncology patients in the US receive care in community settings, where disease specialization is uncommon. To that end, in the US, we do not have any type of lung cancer-specific nursing organization.

Interestingly, in other countries, these organizations exist. For example, in the UK, there is the National Lung Cancer Forum for Nurses (NLCFN), a very active organization that, for the past 17 years, has held annual conferences. Likewise, the Australian New Zealand Lung Cancer Nurses Forum (ANZ-LCNF) has held an annual conference 6 years running.

The International Thoracic Oncology Nursing Forum (ITONF) is a recently formed organization that aims to bring together lung cancer nurses from around the world and provide a platform and resources for lung cancer nurses. The ITONF provides a CE-accredited halfday workshop at the IASLC World Conference on Lung Cancer (WCLC) for nurses and other allied health care providers attending the conference. This year, it will take place on December 4, 2016 at the Messe Wien Exhibition and Congress Center in Vienna, Austria, 7:30 am-12 noon, with breakfast included.

Please visit www.itonf.com for more information regarding registration.

Recognizing the growing role of nurse practitioners and other allied health care professionals, IASLC, three years ago,

2016

Lung Cancer

“ In the US, we do not have any type of lung cancer-specific nursing organization. ” –Beth Eaby-Sandy, MSN, CRNP, OCN

Mee tings Calendar April IASLC and ESMO Present 6th European Lung Cancer Conference April 13–16

formed the IASLC Nurses and Allied Health Professional (AHP) Committee with the aim of enhancing multiple core objectives of IASLC, including the promotion of education, research and science, organizational growth, professional membership, charitable giving and philanthropic relationships, and operational soundness. The main responsibilities of the Nurses and AHP subgroup are to increase nursing and AHP attendance at WCLC, to strengthen IASLC’s communication plan to nurses and AHPs, to focus on developing education strategy to reach all nurses and AHPs working in lung cancer across the globe, to promote research activity and support, and to increase membership of nurses and AHP. The committee membership is evolving and now includes representatives from key national and international nursing organizations.

John White, RN, from LEEDS hospital in the UK has taken over as the chair of the Nurses and AHP Committee.

In this role he will lead efforts to integrate nursing and other allied health care professionals into the curriculum for IASLC and the WCLC. Currently,

White leads the Macmillan Lung Cancer Nurse Specialist team, which consists of 5 nurse specialists. The cancer unit sees around 550 new lung cancer patients every year, with its main focus on supporting patients from the time cancer is first diagnosed, through clinical investigations, treatment, survivorship, and end-of-life care. They have a very close working relationship with respiratory physicians, oncologists, thoracic surgeons, and palliative care teams on-site.

The team is research-active and has just received institutional review board (IRB) approval to run a trial examining the potential benefits of yoga following thoracic surgery. His experience as a professional in this field will greatly benefit IASLC.

Geneva, Switzerland Workshop in Lung Cancer Clinical Research for LATAM Region April 28–30 Santiago, Chile

MAY IASLC Asia Pacific Lung Cancer Conference (APLCC) May 13–16 Chiang-Mai, Thailand

JUNE American Society of Clinical Oncology (ASCO) June 3–7 Chicago, IL, US

august 17th Annual International Lung Cancer Congress August 4–6 Huntington Beach, CA, US

John White, RN, chair of the Nurses and AHP Committee.

Latin American Lung Cancer Conference (LALCA) August 25–27 Panama City, Panama

september

Beth Ivimey presents at the ITONF workshop at WCLC in Denver 2015.

This brings up a dilemma. Where do lung cancer nurses and AHPs go for continuing education and networking?

In the US, the Oncology Nursing Society (ONS) and the Advanced Practitioner Society for Hematology and Oncology (APSHO) are two organizations with excellent annual conferences as well as publications and regional symposia.

However, they are generalized oncology organizations and not specific to lung cancer. Although they serve the needs of most of the oncology nursing and AHP community in the US, as we look forward, there will undoubtedly be increasing specialization in oncology care by disease site and a need for more specialized educational platforms.✦

IASLC Chicago Multidisciplinary Symposium in Thoracic Oncology September 22–24 Chicago, IL, US

december World Conference on Lung Cancer December 4–7 Vienna, Austria

January 2017 Best of WCLC, Seoul January 16, 2017 Seoul, South Korea

IASLC Lung Cancer News / APRIL 2016

15

Names and News Alex A. Adjei, MD, PhD, FACP, has been appointed Professor of Oncology at Mayo Clinic, Rochester, US. He is also Director of the Early Cancer Therapeutics Program and Director of Global Oncology at Mayo’s three sites in Arizona, Florida, and Minnesota.

Dr. Adjei is Editor-in-Chief of the Journal of Thoracic Oncology and previously was Professor and Chair of the Department of Medicine and the Katherine Anne Gioia Chair in Cancer Medicine at Roswell Park Cancer Institute.

Dr. Federico Cappuzzo, MD, PhD, has been appointed as the new Director of Medical Oncology at Azienda Unità Sanitaria Locale (AUSL) della Romagna in Ravenna, Italy.

Dr. Cappuzzo was previously the Director of the Medical Oncology Department at the Ospedale Civile, Livorno.

Bruce E. Johnson, MD, FASCO, has been elected President of the American Society of Clinical Oncology (ASCO) for the term beginning in June 2017. Dr. Johnson is Chief Clinical Research Officer and Institute Physician at the Dana-Farber Cancer Institute, Boston, US, Professor of Medicine at Harvard Medical School, and Director of the Dana-Farber/Harvard Cancer Center Lung Cancer Program.

Karen Kelly, MD, has been named chair of the Lung Committee of SWOG, one of the US’s leading cooperative cancer research organizations. Dr. Kelly is Professor of Medicine, holds the Jennifer Rene Harmon Tegley and Elizabeth Erica Harmon Endowed Chair in Cancer Clinical Research, and is the Associate Director for Clinical Research at at the UC Davis Comprehensive Cancer Center, Sacramento, US.

Lee M. Krug, MD has taken a position as the Immuno-Oncology Disease Area Head for Lung and Head & Neck Cancers in US Medical at Bristol-Myers Squibb. He assumes this role following 15 years on the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center where he focused his clinical research primarily in small-cell lung cancer and mesothelioma.

Prof Sylvie Lantuejoul moved in May 2015 to Centre Léon Bérard, a cancer institute under the aegis of the Unicancer Consortium in Lyon, France. She continues as Professor in Pathology at the Grenoble Alpes University.

Prof Lantuejoul also works for the National Reference Center, MESOPATH-dir Pr F Galateau-Sallé, a French network dedicated to the diagnosis of mesothelioma and rare tumors of the peritoneum and translational research in these diseases.

Suresh S. Ramalingam, MD, has been appointed Deputy Director of Winship Cancer Institute of Emory University and Assistant Dean for Cancer Research in the Emory School of Medicine, Atlanta, US. Dr. Ramalingam previously was Director of Medical Oncology at Winship and its Lung Cancer Program, and co-led Winship’s Discovery and Developmental Therapeutics Program. He is also the Chair of the ECOG-ACRIN Cancer Research Group Thoracic Committee.

Ravi Salgia, MD, PhD has been appointed Chair for the Department of Medical Oncology and Therapeutics Research and the Associate Director for Clinical Sciences in City of Hope's Comprehensive Cancer Center, Duarte, US. Dr. Salgia was on faculty at the Dana-Farber Cancer Institute for a decade and then moved to the University of Chicago as the Director of Thoracic Oncology Program, where he served as Professor of Medicine, Pathology, and Dermatology.

Joan H. Schiller, MD, has been appointed Deputy Director for Clinical Investigation at the Inova Schar Cancer Institute, Falls Church, US. Dr. Schiller was previously the Professor and Chief, Hematology/Oncology Division at the UT Southwestern Harold C. Simmons Comprehensive Cancer Center.

Frances A. Shepherd, MD, FRCPC, has been appointed as an Officer of the Order of Canada for her leadership in improving treatment options and outcomes for individuals with advanced lung cancer. Dr. Shepherd is Senior Staff Physician at The Princess Margaret Cancer Centre, Toronto, Canada, where she holds the Scott Taylor Chair in Lung Cancer Research. She is Full Professor of Medicine at the University of Toronto.

are invited to submit new content for a future Names and News column to Editor@iaslclungcancernews.net; ➲ Readers submissions received will be subject to review and approval by the Editor, and selection for publication is not guaranteed.

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17TH WORLD CONFERENCE ON LUNG CANCER

THE DATE!

December 4â&#x20AC;&#x201C;7, 2016 vienna, austria conference president: robert pirker, md

WWW.IASLC.ORG

TOGETHER AGAINST LUNG CANCER

IMPORTANT DATES Online Registration & Housing

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JULY 15, 2016

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SEPTEMbER 14, 2016

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SEPTEMbER 23, 2016

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OCTObER 15, 2016

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OCTObER 21, 2016