Lung Cancer CME ACCREDITED Watch Time: 42 mins

touchEXPERT OPINIONS Current treatment paradigm and future prospects for extensive-stage small cell lung cancer in the relapsed setting

Watch three oncology specialists discuss the latest advances in the treatment of extensive-stage small cell lung cancer (SCLC).

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Prof. Taofeek Owonikoko
Emory University School of Medicine, Georgia, USA
The current treatment paradigm of extensive-stage small cell lung cancer

Prof. Taofeek Owonikoko discusses recent changes in the treatment landscape of extensive-stage small cell lung cancer and the challenges associated with identifying therapeutic targets in this disease.

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Interview Questions

In this interview, Prof. Taofeek Owonikoko answers the following questions:

  • Why is there a need for novel first-line treatment approaches in extensive-stage small cell lung cancer?
  • How has the addition of checkpoint inhibitors impacted the treatment landscape in extensive-stage small cell lung cancer?
  • Why is the development of targeted agents a challenge in small cell lung cancer?
  • What other therapeutic mechanisms can be used to manage extensive-stage small cell lung cancer?
  • How will the updated National Comprehensive Cancer Network (NCCN) guidelines impact patient management and outcomes in extensive-stage small cell lung cancer?
About Prof. Taofeek Owonikoko

Prof. Taofeek Owonikoko is Professor and Vice Chair for Faculty Development in the Department of Hematology and Medical Oncology at Emory University. He is also a Georgia Research Alliance Distinguished Cancer Scientist. read more

Prof. Owonikoko has been part of the faculty at Emory University since 2008 and has focused his translational research activities on lung cancer, thyroid cancer and early-phase drug development.

Prof. Owonikoko has received peer-reviewed grant funding from the National Institute of Health, Department of Defense and Georgia Cancer Coalition. He has published over 219 peer-reviewed manuscripts in high-impact journals including New England Journal of Medicine, Cell, Science, Nature, CA Cancer Journal, Cancer Cell, Lancet Oncology, Journal of Clinical Oncology, Cancer Discovery, Nature Communications, Oncogene, Cancer Research, Clinical Cancer Research and Journal of Thoracic Oncology.

Prof. Owonikoko discloses (as of September 2020): Research support (to institution) from Aeglea Biotherapeutics, Amgen, Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers, Eisai, Fujifilm, G1 Therapeutics, Incyte, Ipsen, Loxo/Lilly, Merck, Mersana, Novartis, Oncorus, Pfizer, Regeneron, Roche/Genentech , StemCentRx, Turning Point and United Therapeutics; Consulting/advisory board fees from Abbvie, Amgen, ARMO BioSciences, AstraZeneca, Bayer, BerGenBio, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, EMD Serono, G1 Therapeutics, Heron Pharmaceutical, Ipsen, Jazz, Lilly, MedImmune, Merck, Novartis, PharmaMar, Sandoz, XCovery and Zentalis; Independent review committee/data safety monitoring board fees from EMD Serono and Roche/Genentech; Stockholdings /co-founder of Cambium Oncology.

 
Dr Viola Zhu
University of California Irvine, California, USA
New treatment options in the second-line and beyond for small cell lung cancer

Dr Viola Zhu reviews the evidence behind US Food and Drug Administration (FDA) approvals of targeted treatments for relapsed small cell lung cancer and implications for patient management.

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Interview Questions

In this interview, Dr Viola Zhu answers the following questions:

  • What is the evidence base for the accelerated FDA approval of second-line lurbinectedin in extensive-stage small cell lung cancer?
  • What evidence led to the approval of nivolumab in the third-line setting and its subsequent withdrawal from the US market?
  • What are the key data that led to the accelerated approval of pembrolizumab in the third-line setting?
  • What adverse events may be experienced with immune checkpoint inhibitors and lurbinectedin?
  • How are adverse events that are associated with immune checkpoint inhibitors and lurbinectedin best managed in clinical practice?
About Dr Viola Zhu

Dr Viola Zhu is Associate Clinical Professor of Medicine at the University of California Irvine and an attending physician at the Chao Family Comprehensive Cancer Center. read more

Dr Zhu earned her medical degree from Fudan University Shanghai Medical College (formerly Shanghai Medical University) and was in a graduate programme in Medical Oncology at the Fudan University Shanghai Cancer Center prior to receiving her PhD degree in Molecular Pathology and Immunology from the University of Medicine and Dentistry of New Jersey. She completed her residency in Internal Medicine at Englewood Hospital and Medical Center and fellowship in Hematology and Oncology at Boston Medical Center. She is board-certified in Internal Medicine, Hematology and Medical Oncology.

Dr Zhu’s clinical focus is lung cancer, and she is actively involved in many early-phase trials of novel targeted therapies. She is on the editorial board for Journal of Clinical Oncology and has publications in many high-impact journals including New England Journal of Medicine, Journal of Clinical Oncology, and Cancer Discovery.

Dr Viola Zhu discloses: Consultancy/advisory board fees from AstraZeneca, Roche/Genentech, Takeda, Xcovery; Stockholdings in TP Therapeutics (until May 2020); Speakers bureau fees from AstraZeneca, Blueprint, Roche/Genentech and Takeda.

 
Prof. Giuseppe Giaccone
Weill Cornell Medical Center,
New York, USA
Future prospects in the treatment of small cell lung cancer in the relapsed setting

Prof. Giuseppe Giaccone outlines the emerging molecular classification of small cell lung cancer, and potential therapeutic approaches and biomarkers currently being investigated in this disease.

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Interview Questions

In this interview, Prof. Giuseppe Giaccone answers the following questions:

  • How can molecular classification of small cell lung cancer facilitate the development of new therapeutic approaches?
  • What therapeutic targets and treatment strategies are being explored in small cell lung cancer?
  • What emerging targets show promise in relapsed small cell lung cancer?
  • What immunotherapy combination approaches are being explored in relapsed small cell lung cancer?
  • What biomarkers are being investigated to help guide treatment selection for patients with small cell lung cancer?
About Prof. Giuseppe Giaccone

Prof. Giuseppe Giaccone is an internationally recognized expert in the field of lung cancer and developmental therapeutics. In September 2019, he joined Weill Cornell Medicine and New York-Presbyterian Hospital as Chief of Thoracic Oncology and Associate Director for Clinical Research at the Sandra and Edward Meyer Cancer Center. He also directs the phase I clinical trial programme for early drug development. read more

Prof. Giaccone played an influential role at the European Organization for Research and Treatment of Cancer (EORTC), serving as a member of the EORTC’s Lung Cancer Cooperative Group since 1982 and as its Chair from 1993 to 2000. He also led several major clinical studies focusing on lung cancer and other thoracic tumours.

Prof. Giaccone was appointed Chief of the Medical Oncology Branch of the Center for Cancer Research of the National Cancer Institute in April 2007. In 2013, Prof. Giaccone joined the Lombardi Comprehensive Cancer Center at Georgetown University in Washington, DC as the Associate Director for Clinical Research and the Director of Clinical Research for the MedStar Health Cancer Network’s Washington Region, and Professor of Medical Oncology and Pharmacology.

Prof. Giaccone’s research is mainly focused on the study of the biology of lung cancer and thymic tumours, and treatment of these tumour types. He has made seminal discoveries that have led to new ways of treating lung cancer and diagnosing thymic tumours. Prof. Giaccone has published more than 500 peer-reviewed papers and contributed to more than 30 book chapters.

Prof. Giuseppe Giaccone has no financial interests/relationships of affiliations to disclose in relation to this activity.

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Overview & Learning Objectives
Overview

In this activity, three leading experts discuss the evolving treatment landscape of extensive-stage SCLC and review the latest clinical trial data for emerging therapies in this field.

This activity has been jointly provided by Oakstone and touchIME ONCOLOGY. Oakstone Publishing is accredited by the ACCME to provide continuing medical education to physicians.

Target audience

This activity has been designed to meet the educational needs of oncology specialists involved in the management of patients with small cell lung cancer.

Disclosures

Oakstone Publishing has assessed conflict of interest with its faculty, authors, editors, and any individuals who were in a position to control the content of this CME activity. Any identified relevant conflicts of interest were resolved for fair balance and scientific objectivity of studies utilized in this activity. Oakstone Publishing’s planners, content reviewers, and editorial staff disclose no relevant commercial interests.

Faculty

Prof. Owonikoko discloses (as of September 2020): Research support (to institution) from Aeglea Biotherapeutics, Amgen, Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers, Eisai, Fujifilm, G1 Therapeutics, Incyte, Ipsen, Loxo/Lilly, Merck, Mersana, Novartis, Oncorus, Pfizer, Regeneron, Roche/Genentech , StemCentRx, Turning Point and United Therapeutics; Consulting/advisory board fees from Abbvie, Amgen, ARMO BioSciences, AstraZeneca, Bayer, BerGenBio, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, EMD Serono, G1 Therapeutics, Heron Pharmaceutical, Ipsen, Jazz, Lilly, MedImmune, Merck, Novartis, PharmaMar, Sandoz, XCovery and Zentalis; Independent review committee/data safety monitoring board fees from EMD Serono and Roche/Genentech; Stockholdings /co-founder of Cambium Oncology.

Dr Viola Zhu discloses: Consultancy/advisory board fees from AstraZeneca, Roche/Genentech, Takeda, Xcovery; Stockholdings in TP Therapeutics (until May 2020); Speakers bureau fees from AstraZeneca, Blueprint, Roche/Genentech and Takeda.

Prof. Giuseppe Giaccone has no financial interests/relationships of affiliations to disclose in relation to this activity.

Content reviewer

Walter Murray Yarbrough, MD, FACP has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Hennah Patel, MPharm, RPh, has no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Oakstone Publishing and touchIME. Oakstone Publishing is accredited by the ACCME to provide continuing medical education for physicians.

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 Credit™ into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

Oakstone Publishing designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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

Date of original release: 25 March 2021. Date credits expire: 25 March 2022.

Learning Objectives

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

  • Summarize the current treatment recommendations for SCLC and how they are evolving as new agents emerge
  • Evaluate the efficacy and safety of emerging agents for relapsed SCLC
  • Describe emerging treatment options and ongoing clinical trials for relapsed SCLC
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Question 1/5
Your patient receives a primary diagnosis of ES-SCLC. What would be your preferred systemic therapy regimen?
Correct

The NCCN Guidelines for SCLC recommend either atezolizumab or durvalumab plus platinum chemotherapy (cisplatin or carboplatin) plus etoposide as primary therapy for ES-SCLC, followed by maintenance atezolizumab or durvalumab. Four cycles of therapy are recommended, but some patients may receive up to six cycles based on response and tolerability after four cycles.1
In the clinical trials of first-line atezolizumab or durvalumab + platinum chemotherapy–etoposide in ES-SCLC, patients received four cycles of treatment.2,3

  • In the atezolizumab study the platinum chemotherapy administered was carboplatin.2
  • In the durvalumab study, the investigators’ choice of either carboplatin or cisplatin was administered. Furthermore, an additional two cycles of platinum chemotherapy–etoposide were allowed in the control arm.3

Abbreviations: ES-SCLC, extensive-stage small cell lung cancer; NCCN, National Comprehensive Cancer Network; SCLC, small cell lung cancer.

References:

1. NCCN Guidelines. Small-cell lung cancer. Version 2, 2021. Available at: www.nccn.org/professionals/physician_gls/pdf/sclc.pdf (accessed 26 February 2021).
2. Horn L, et al. N Engl J Med. 2018;379:2220–9.
3. Paz-Ares L, et al. Lancet. 2019;394:1929–39.

Question 2/5
Which of the following statements best describes outcomes from the clinical trial that led to FDA approval of lurbinectedin in second-line ES-SCLC?
Correct

Single-agent lurbinectedin is FDA approved for the treatment of adult patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy.1 Approval was granted based on results from a phase II, open-label, multi-centre, basket trial (NCT02454972) in patients with advanced solid tumours.2,3 The ORR in the SCLC patient population (n=105) was 35% and the median DOR was 5.3 months. The most common grade 3–4 AEs were haematological in nature.2
Lurbinectedin is also being evaluated in combination with doxorubicin for the treatment of adult patients with SCLC with disease progression after one prior line of platinum-based chemotherapy, in the multi-centre, randomized, controlled, phase III ATLANTIS trial.4

Abbreviations:
AE, adverse event; DOR, duration of response; ES-SCLC; extensive-stage small cell lung cancer; FDA, US Food and Drug Administration; ORR, overall response rate; SCLC, small cell lung cancer.

References:
1. FDA. FDA grants accelerated approval to lurbinectedin for metastatic small cell lung cancer. 16 June 2020. Available at: www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-lurbinectedin-metastatic-small-cell-lung-cancer (accessed 26 February 2021).
2. Trigo J, et al. Lancet Oncol. 2020;21:645–54.
3. ClinicalTrials.gov Identifier NCT02454972. Available at: clinicaltrials.gov (accessed 26 February 2021).
4. ClinicalTrials.gov Identifier NCT02566993. Available at: clinicaltrials.gov (accessed 26 February 2021).

Question 3/5
Two months after commencing therapy with an immune checkpoint inhibitor, your patient with ES-SCLC reports symptoms of rash and itching. Upon examination you classify the symptoms as grade 2 skin side-effects. According to ASCO Practice Guideline recommendations, how will you manage this patient?
Correct

ASCO Practice Guidelines note that for patients treated with immune checkpoint inhibitors, there should be a high level of suspicion that new symptoms are treatment related. Management of immune-mediated side effects may require referral to a specialist.
In general, immune checkpoint inhibitor therapy should be continued with close monitoring for grade 1 toxicities, apart from some neurologic, haematologic, and cardiac toxicities. Treatment may need to be suspended for patients with grade 2 symptoms and corticosteroids may be administered until symptoms have subsided or resolved. For patients with grade 3 symptoms, therapy should be suspended and high-dose corticosteroids initiated. For grade 4 symptoms, treatment typically will be permanently discontinued.

Abbreviation: ASCO, American Society of Clinical Oncology.

Reference:

Brahmer J, et al. J Clin Oncol. 2018;36:1714–68.

Question 4/5
Which molecular subtype of SCLC has been found to experience the greatest benefit from the addition of immunotherapy to chemotherapy?
Correct

SCLC-I experiences the greatest benefit from the addition of immunotherapy to chemotherapy, while the other subtypes each have distinct vulnerabilities, including to inhibitors of PARP, aurora kinases, or BCL-2.

Abbreviations:
BCL-2, B-cell lymphoma 2; PARP, poly-ADP ribose polymerase; SCLC, small cell lung cancer.

Reference:

Gay CM, et al. Cancer Cell. 2021;39:1–15.

Question 5/5
Which of the following is true regarding clinical trials currently investigating (March 2021) targeted approaches in ES-SCLC?
Correct

A number of therapeutic targets and treatment strategies are being explored in clinical trials in SCLC.1 For example:
The phase III SKYSCRAPER-02 trial aims to investigate atezolizumab (PD-L1 inhibitor) + carboplatin + etoposide ± tiragolumab (TIGIT inhibitor) in first-line ES-SCLC (NCT04256421).2
The phase III ATLANTIS trial is evaluating lurbinectedin (RNA polymerase II inhibitor) + doxorubicin in second-line SCLC (NCT02566993).3

Abbreviations: ES-SCLC, extensive-stage small cell lung cancer; PD-L1, programmed death ligand 1; RNA, ribonucleic acid; SCLC, small cell lung cancer; TIGIT, T cell inhibitory receptor.

References:
1. Taniguchi H, et al. Front Oncol. 2020;10:741.
2. ClinicalTrials.gov Identifier NCT04256421. Available at: clinicaltrials.gov (accessed 26 February 2021).
3. ClinicalTrials.gov Identifier NCT02566993. Available at: clinicaltrials.gov (accessed 26 February 2021).

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