Lung Cancer, Immunotherapy CE/CME ACCREDITED Watch Time: 35 mins

touchPANEL DISCUSSION Exploring the latest advances in first-line treatment of ES-SCLC: Translating the data to clinical practice

Watch leading lung cancer experts share their insights on the latest advancements in first-line treatment of extensive-stage small cell lung cancer (ES-SCLC).

Dr Marina Garassino

University of Chicago, Chicago, IL, USA

CHAIR
Panelists:
Dr Luis Paz-Ares, Dr Martin Edelman
 
Video Chapters
Introduction

Dr Garassino introduces the faculty for this activity.

view bio and disclosures 1/4 Next Chapter
 
Advances in the first-line treatment of ES-SCLC: Where are we now?

The expert panel discuss the clinical trial data on the use of immunotherapy in the first-line treatment of ES-SCLC and how they have changed clinical practice and patient outcomes.

view bio and disclosures 2/4 Next Chapter
 
Exploring safety with immunotherapy combinations: How can we mitigate side effects?

The expert faculty consider the safety profile of immunotherapy combinations for first-line treatment of ES-SCLC and how side effects can be managed in daily practice.

view bio and disclosures 3/4 Next Chapter
 
Emerging therapies for ES-SCLC: What is on the horizon?

The chair and panelists review ongoing clinical trials for emerging therapies for ES-SCLC and how biomarkers and molecular subtyping might help to guide treatment decisions in the future.

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Overview & Learning Objectives
Overview

In this activity, three leading experts share their perspectives on recent advances in the first-line treatment of ES-SCLC, the safety profiles of immunotherapy combinations and how to manage side effects, and the direction in which the field is moving with emerging therapies and prognostic biomarkers.

This activity is jointly provided by USF Health and touchIME. read more

Target Audience

This activity has been designed to meet the educational needs of oncologists, including lung cancer specialists, pulmonologists and radiation oncologists, involved in the management of ES-SCLC.

Disclosures

USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity.  The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

Faculty

Dr Marina Garassino discloses: Advisory board or panel fees from AstraZeneca, Boehringer Ingelheim Italia S.p.A, Bristol Myers Squibb, Celgene, Eli Lilly, Ignyta, Incyte, MedImmune, Merck, Mirati, MSD International GmbH, Novartis, Pfizer (MISP), Regeneron, Roche, Tiziana and Takeda. Consultancy fees from AstraZeneca, Boehringer Ingelheim Italia S.p.A, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, Inivata, MedImmune, Merck, Mirati, MSD International GmbH, Novartis, Pfizer, Regeneron, Roche, SeaGen and Takeda.

Dr Luis Paz-Ares discloses: Advisory board or panel fees from AstraZeneca, Janssen, Merck and Mirati. Speaker’s bureau fees from Amgen, AstraZeneca, Bayer, Beigen, Bristol Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Janssen, Eli Lilly, Merck, Mirati, MSD, Novartis, Pfizer, Pharmamar, Roche, Sanofi, Servier and Takeda.

Dr Martin Edelman discloses: Advisory board or panel fees from Biomarker Strategies, Creatv, Novocure, Regeneron/Sanofi and Windmil. Consultancy fees from Flame Biosciences, Kanaph, Novocure and Proventus. Grants/Research Support (all fees to institution) from Amgen, GlaxoSmithKline, Nektar and Windmil. Other financial or material support (member of data safety monitoring boards) from AstraZeneca, SeaGen and Takeda. Stock/shareholder (self-managed) from Biomarker Strategies, Creatv and Microtech.

Content reviewer

Angela Massey Hill, Pharm.D., CPh, RPh. has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Directors

Adriano Boasso and Kathy Day have no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

If you have questions regarding credit please contact cpdsupport@usf.edu.

Accreditations

Physicians

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 a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

Advanced Practice Providers

Physician Assistants may claim a maximum of 0.75 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Date of original release: 4 August 2022. Date credits expire: 4 August 2023.

If you have any questions regarding credit please contact cpdsupport@usf.edu.

Learning Objectives

After watching this activity, participants should be better able to:

  • Recall the latest data on the efficacy of ICI-combination approaches for ES-SCLC in the first-line setting
  • Describe the latest safety data for ICI-combination approaches for patients with ES-SCLC
  • Discuss ongoing ICI clinical trial data and preclinical trials in ES-SCLC
Faculty & Disclosures
Dr Marina Garassino

University of Chicago, Chicago, IL, USA

Dr Marina Garassino is professor of medicine in the Department of Medicine, Section of Hematology Oncology at the University of Chicago, IL, USA. Until February 2021, she was the chief of the Thoracic Oncology Unit at the Istituto Nazionale dei Tumori, Milano, Italy. read more

Dr Garassino has been an active researcher in precision medicine and in immuno-oncology. Her main research interests have been the development of new drugs, novel therapeutic strategies and biomarkers. She has contributed to over 200 peer-reviewed publications, including publications as first or senior author in the New England Journal of Medicine, Lancet Oncology, Journal of Clinical Oncology and Annals of Oncology. She has delivered several presentations at international congresses such as  the American Society of Clinical Oncology (ASCO), the European Society of Medical Oncology (ESMO), the European Congress on Clinical Oncology (ECCO), the World Conference on Lung Cancer (WCLC) and the American Association for Cancer Research (AACR).

Dr Marina Garassino discloses: Advisory board or panel fees from AstraZeneca, Boehringer Ingelheim Italia S.p.A, Bristol Myers Squibb, Celgene, Eli Lilly, Ignyta, Incyte, MedImmune, Merck, Mirati, MSD International GmbH, Novartis, Pfizer (MISP), Regeneron, Roche, Tiziana and Takeda. Consultancy fees from AstraZeneca, Boehringer Ingelheim Italia S.p.A, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, Inivata, MedImmune, Merck, Mirati, MSD International GmbH, Novartis, Pfizer, Regeneron, Roche, SeaGen and Takeda.
Dr Luis Paz-Ares

Hospital Universitario 12 de Octubre, Complutense University and Ciberonc, Madrid, Spain

Dr Luis Paz-Ares is chair of the Medical Oncology Department at the Hospital Universitario 12 de Octubre, associate professor at the Universidad Complutense and head of the Lung Cancer Unit at National Oncology Research Center, all in Madrid, Spain. read more

Before his current position, he was chair of the Medical Oncology Department at the Virgen del Rocío University Hospital in Seville (2007–2014), head of the Pharmacology Unit and responsible for Early Clinical Studies of Thoracic and Genitourinary Tumours at the University Hospital 12 de Octubre in Madrid (1995–1999; 2000–2007), and visiting research fellow in the Prostate Cancer Program at the Dana-Farber Cancer Institute in Boston, MA, USA (1999–2000).

Dr Paz-Ares’s research focuses on lung cancer and the development of new therapeutic strategies at both preclinical and clinical level. He has published more than 340 articles in peer-reviewed journals, including the New England Journal of Medicine, Lancet, Lancet Oncology, Nature Medicine and Journal of Clinical Oncology. He has served as a member of the scientific committees for the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) meetings, the European Organisation for Research and Treatment of Cancer (EORTC) Protocol Review Committee and Audit Committee, the Spanish Agency of Medicines and Medical Devices (AEMPS) and the European Medicines Agency (EMA). He is the chief medical officer and board member of the Spanish Association Against Cancer (AECC).

Dr Luis Paz-Ares discloses: Advisory board or panel fees from AstraZeneca, Janssen, Merck and Mirati. Speaker’s bureau fees from Amgen, AstraZeneca, Bayer, Beigen, Bristol Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Janssen, Eli Lilly, Merck, Mirati, MSD, Novartis, Pfizer, Pharmamar, Roche, Sanofi, Servier and Takeda.
Dr Martin J Edelman

Fox Chase Cancer Center, Philadelphia, PA, USA

Dr Martin Edelman is the G Morris Dorrance professor and chair of the Department of Hematology/Oncology and deputy director of clinical research at the Fox Chase Cancer Center in Philadelphia, PA, USA. read more

Dr Edelman has been active in the US National Clinical Trials Network as the medical oncology co-chair for the Lung Cancer Committee and a member of the Eastern Cooperative Oncology Group (ECOG) Lung Cancer Committee. He is a member of the Thoracic Malignancies Steering Committee of the National Cancer Institute (NCI). He has also served as the chair of the Integration Panel for the Department of Defense (DOD) Congressionally Mandated Research Program for lung cancer.  He is a past chair of the Ethics Committee and the Career Development Committee and a member of the Communications Committee of the International Association for the Study of Lung Cancer (IASLC) and a deputy editor of the journal Lung Cancer.  Dr Edelman was appointed as chair of the Scientific Advisory Board for the Lung Cancer Foundation of America in February 2018. He has published over 200 peer-reviewed papers in the field. He completed his naval service with the rank of Captain (ret.), United States Navy Reserve (USNR) in 2004.

Dr Martin Edelman discloses: Advisory board or panel fees from Biomarker Strategies, Creatv, Novocure, Regeneron/Sanofi and Windmil. Consultancy fees from Flame Biosciences, Kanaph, Novocure and Proventus. Grants/Research Support (all fees to institution) from Amgen, GlaxoSmithKline, Nektar and Windmil. Other financial or material support (member of data safety monitoring boards) from AstraZeneca, SeaGen and Takeda. Stock/shareholder (self-managed) from Biomarker Strategies, Creatv and Microtech.
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This Activity Is Funded By:

This activity is funded by an independent medical education grant from AstraZeneca. This activity is jointly provided by USF Health and touchIME.

The information provided by this CME activity is for continuing education purposes only and is not meant to substitute for the independent medical/clinical judgment of a healthcare provider relative to diagnostic and treatment options of a specific patient’s medical condition.

USF is an Equal Opportunity / Affirmative Action / Equal Access Institution.

USF Health is accredited by the Accreditation Council for Continuing Medical Education, the American Nurses Credentialing Center and the Accreditation Council for Pharmacy Education to provide continuing education to healthcare professionals. As an accredited provider, USF Health is required to disclose personal information to relevant accredited bodies that certify CME to process credits/contact hours, comply with reporting requirements, and for internal recordkeeping and regulatory purposes. USF Health does not share or sell any individual’s contact information or unique identifiers to any commercial supporter, advertiser, or third party without the specific permission of the individual.

Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. The presenting faculty have been advised by touchIME and USF Health to ensure that they disclose any such references made to unlabelled or unapproved use. No endorsement by touchIME or USF Health of any unapproved products or unapproved uses is either made or implied by mention of these products or uses in touchIME or USF Health activities. touchIME and USF Health accept no responsibility for errors or omissions.

This content is intended for healthcare professionals.

Date of original release: 4 August 2022. Date credits expire: 4 August 2023.

This content is intended for healthcare professionals only. Please confirm that you are a healthcare professional.

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Question 1/5
Your 55-year-old patient has been diagnosed with ES-SCLC and has not yet received treatment. He has adequate organ and bone marrow function, and has no history of active autoimmune disease. Out of the following options, which would you consider the most appropriate first-line treatment?

ES-SCLC, extensive-stage small cell lung cancer.
Correct

The PD-L1 inhibitor durvalumab in combination with etoposide and either carboplatin or cisplatin is approved and recommended for the first-line treatment of ES-SCLC.1,2 Atezolizumab is approved for the first-line treatment of ES-SCLC if used in combination with etoposide and carboplatin, not as monotherapy.3

The PD-1 inhibitors pembrolizumab and nivolumab are not approved for the first-line treatment of ES-SCLC.4,5

Abbreviations

ES-SCLC, extensive-stage small cell lung cancer; FDA, US Food and Drug Administration; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; PI, prescribing information.

References

  1. Ganti AK, et al. J Natl Compr Canc Netw. 2021;19:1441–64.
  2. FDA. Durvalumab PI. 2022. Available at: www.accessdata.fda.gov/scripts/cder/daf/index.cfm (accessed 13 July 2022).
  3. FDA. Atezolizumab PI. 2022. Available at: www.accessdata.fda.gov/scripts/cder/daf/index.cfm (accessed 13 July 2022).
  4. FDA. Pembrolizumab PI. 2022. Available at: www.accessdata.fda.gov/scripts/cder/daf/index.cfm (accessed 13 July 2022).
  5. FDA. Nivolumab PI. 2022. Available at: www.accessdata.fda.gov/scripts/cder/daf/index.cfm (accessed 13 July 2022).
Question 2/5
What did the results of the IMpower133 trial of atezolizumab + EC versus placebo + EC for first-line treatment of ES-SCLC show?

EC, etoposide-carboplatin; ES-SCLC, extensive-stage small cell lung cancer; OS, overall survival; PFS, progression-free survival.
 Correct

The primary endpoints for the IMpower133 trial (NCT02763579) were OS and PFS. 

Median PFS was 5.2 months for atezolizumab + EC versus 4.3 months for placebo + EC (HR 0.77; 95% CI 0.62–0.96).

Median OS was 12.3 months for atezolizumab + EC versus 10.3 months for placebo + EC (HR 0.76; 95% CI 0.60–0.95).

Abbreviations

EC, etoposide-carboplatin; HR, hazard ratio; OS, overall survival; PFS, progression-free survival.

Reference

Liu SV, et al. J Clin Oncol. 2021;39:619–30.

Question 3/5
Your patient is a 71-year-old man with ES-SCLC who is receiving durvalumab + EP chemotherapy and is complaining of palpitations and dyspnoea. How do you proceed?

ECG, electrocardiogram; EP, etoposide-platinum; ES-SCLC, extensive-stage small cell lung cancer; MRI, magnetic resonance imaging.
 Correct

Myocarditis is a rare but potentially life-threatening side effect of ICIs, including durvalumab and atezolizumab.1 

Typical presentation of moderate myocarditis includes chest pain, dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, palpitations and fatigue.2 The diagnostic work-up for ICI-induced myocarditis includes measurement of troponin serum levels, EGC and MRI.2 Treatment with ICI should be stopped while the diagnosis of myocarditis is confirmed.2 The FDA recommends permanent discontinuation of durvalumab for patients who develop grade 2, 3 or 4 myocarditis.3

Abbreviations

ECG, electrocardiogram; FDA, US Food and Drug Administration; ICI, immune checkpoint inhibitor; MRI, magnetic resonance imaging.

References

  1. Brahmer JR, et al. J Immunother Cancer. 2021;9:e002435.
  2. Palaskas N, et al. J Am Heart Assoc. 2020;9:e013757.
  3. FDA. Durvalumab prescribing information. Available at: www.accessdata.fda.gov/scripts/cder/daf/index.cfm (accessed 27 July 2022).
Question 4/5
When starting a patient with newly diagnosed ES-SCLC on atezolizumab + etoposide-carboplatin, which of the following immune-related side effects would you discuss with your patient as some of the most common but usually manageable?

ES-SCLC, extensive-stage small cell lung cancer.
 Correct

irAEs occurred in approximately 40% of patients who received atezolizumab + EC in the IMpower133 trial.

Commonly occurring irAEs (any grade) included rash (18.7%), hypothyroidism (12.6%), hepatitis (7.1%), infusion-related reaction (5.6%) and hyperthyroidism (5.6%).

Abbreviations

EC, etoposide-carboplatin; irAE, immune-related adverse event.

Reference

Horn L, et al. N Engl J Med. 2018;379:2220–9.

Question 5/5
Before initiating first-line treatment with durvalumab or atezolizumab for your patients with ES-SCLC, for which of the following biomarkers would you test for to predict treatment outcomes?

ES-SCLC, extensive-stage small cell lung cancer; PD-L1, programmed death-ligand 1; TMB, tumour mutational burden.
 Correct

There are currently no validated predictive biomarkers for response to ICIs in ES-SCLC.1 In both the CASPIAN and IMPower-133 trials, response to durvalumab or atezolizumab was independent of PD-L1 expression,2,3 and TMB was not predictive of treatment outcomes.3,4

Abbreviations

ES-SCLC, extensive-stage small cell lung cancer; ICI, immune checkpoint inhibitor; PD-L1, programmed death-ligand 1; TMB, tumour mutational burden.

References

  1. Ortega-Franco A, et al. ESMO Open. 2021;6:100003.
  2. Paz-Ares L, et al. Ann Oncol. 2019;30(Suppl. 5):v928–9.
  3. Liu SV, et al. J Clin Oncol. 2021;39:619–30.
  4. Goldman JW, et al. Ann Oncol. 2020;31(Suppl. 4):S1212–3.
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