Lung Cancer CME ACCREDITED Watch Time: 37 mins

touchEXPERT OPINIONS Moving MET into the clinic: Latest evidence for MET inhibitors in NSCLC

Watch leading experts review the latest clinical data from ASCO 2021 on the role of MET inhibitors in NSCLC and the importance of identifying patients who may benefit from a targeted approach

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Dr Enriqueta Felip
Vall d’Hebron University Hospital, Barcelona, Spain
MET inhibitor clinical efficacy: Update from ASCO 2021

Dr Felip discusses the most recent efficacy data from ASCO 2021 on the use of MET inhibitors in NSCLC

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Interview Questions

In this interview Dr Felip answers the following questions:

  • How significant is MET as a therapeutic target in patients with NSCLC?
  • How do current data support the use of MET-inhibitor therapy in patients with MET+ NSCLC?
  • What were the updated findings at ASCO 2021 for the VISION and GEOMETRY mono-1 studies in patients with MET+ NSCLC?
  • What were the key efficacy findings at ASCO 2021 for MET-inhibitor therapy in patients with advanced NSCLC and MET amplification?
  • How do the latest data affect current use of MET inhibitors in NSCLC and what are the potential future developments?
About Dr Enriqueta Felip

Enriqueta Felip, MD, PhD, is the Head of the Thoracic and Head and Neck Cancer Unit within the Oncology Department of Vall d’Hebron Hospital, Barcelona, Spain, and Professor of Medicine at the Universitat de Vic (UVicc-UCC). read more

Dr Felip is responsible for thoracic cancer trials undertaken by the Oncology Department. Her current research includes the optimization of chemotherapy in early-stage disease, evaluation of new agents and therapies, research into novel pharmacogenomic approaches, the integration of immunotherapeutic approaches in the treatment of lung cancer, and the elucidation of potential mechanisms of resistance to tyrosine-kinase inhibitors.

Dr Felip is currently a member of the Spanish Lung Cancer Group (SLCG) and the Spanish Society of Medical Oncology (SEOM). In October 2019, Dr Felip was elected SEOM Vice-President for 2019–2021.

Dr Felip is also a member of the European Society of Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), and the International Association for the Study of Lung Cancer (IASLC). She is also a member of the Board of Directors of the IASLC (2017–2021). Dr Felip is currently President of the Oncology Commission at Vall d’Hebron University Hospital and a member of the Scientific Advisory Committee of the Parc Taulí Sabadell Hospital. She is also a member of the scientific committee of the SLCG.

Dr Enriqueta Felip discloses: Advisory board fees from Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Merck Serono, Peptomyc, Pfizer, Puma, Regeneron, Sanofi, Syneos Health and Takeda. Invited speaker fees from Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Merck Sharp & Dohme, Merck Serono and Pfizer.

 
Dr Rebecca S Heist
Massachusetts General Hospital, Boston, USA
Moving on to METex14 testing in the clinic

Dr Heist discusses the most recent data from ASCO 2021 on MET testing in NSCLC within the context of current research and recommendations.

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Interview Questions

In this interview Dr Heist answers the following questions:

  • What are the current recommendations for testing METex14 in patients with NSCLC?
  • What are the challenges for testing and how can next-generation sequencing be used optimally to detect METex14?
  • Do data presented at ASCO 2021 further support the use of RNA-sequencing for METex14 testing?
  • What are the pros and cons of using tissue versus liquid biopsy for testing?
  • How do data presented at ASCO 2021 expand our knowledge on the role of liquid biopsy in METex14 NSCLC?
  • What are the key takeaways from ASCO 2021 for NSCLC testing?
About Dr Rebecca Heist

Rebecca Suk Heist, MD, MPH, is an Associate Professor of Medicine at Harvard Medical School and Thoracic Oncologist at Massachusetts General Hospital in Boston, MA. She specializes in thoracic cancer and is experienced in the treatment of lung cancer, with a special focus on clinical trials of novel agents.

Dr Rebecca S Heist discloses: Consulting honoraria from Apollomics, Boehringer Ingelheim, Daichii Sankyo, EMD Serono, Novartis and Takeda. Research funding (to institution, not to self) from Agios, AbbVie, Corvus, Daiichi Sankyo, Eli Lilly, Exelixis, Genentech Roche, Mirati, Novartis and Turning Point.

 
Dr Takashi Seto
National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
Adverse event management and implementation of MET inhibitor therapy

Dr Seto discusses the most recent safety data from ASCO 2021 on the use of MET inhibitors in NSCLC

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Interview Questions

In this interview Dr Seto answers the following questions:

  • What are common adverse events associated with MET inhibitors in patients with METex14 NSCLC?
  • How are adverse events associated with MET inhibitors managed in clinical practice?
  • What were the key safety data updates for MET inhibitors at ASCO 2021, either as monotherapy or in combination with an EGFR inhibitor?
  • Is the risk:benefit profile for the use of immunotherapy acceptable in METex14 NSCLC?
About Dr Takashi Seto

Takashi Seto, MD, is a Medical Oncologist at the National Hospital Organization Kyushu Cancer Center in Japan. read more

Dr Seto is a member of a number of academic societies, including the International Association for Study of Lung Cancer (IASLC, Board of Directors 2017 to 2019), the American Society for Clinical Oncology (ASCO), the European Society of Medical Oncology (ESMO), the Japanese Society of Medical Oncology (JSMO, Councilor), and the Japan Lung Cancer Society (JLCS, Councilor).

He has been involved with the revision of the JLCS Practice Guidelines since 2005 and was a chief of Medical Oncology and Multidisciplinary Therapy from 2014 to 2018. Dr Seto is also an active member of the Japan Clinical Oncology Group (JCOG) and the West Japan Oncology Group (WJOG), and has been involved in developing and conducting numerous clinical trials for lung cancer.

Dr Takashi Seto discloses: Consulting honoraria from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Covidien Japan, Daiichi Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, Mochida Pharmaceutical, MSD, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical and Takeda Pharmaceutical. Research funding from Abbvie, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, LOXO Oncology, Merck Sharp & Dohme, Novartis Pharma, Pfizer Japan and Takeda Pharmaceutical.

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Overview & Learning Objectives
Overview

In this activity, three experts explore the evolving landscape of MET inhibitors in NSCLC, share the latest efficacy and safety data from ASCO 2021 and highlight the importance of testing for METex14 in the clinic.

This activity has been jointly provided by Oakstone and touchIME for touchONCOLOGY. 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 oncologists and respirologists involved in the management of non-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 have been mitigated. Oakstone Publishing’s planners, content reviewers, and editorial staff disclose no relationships with ineligible entities.

Faculty

Dr Enriqueta Felip discloses: Advisory board fees from Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck Sharp & Dohme, Merck Serono, Peptomyc, Pfizer, Puma, Regeneron, Sanofi, Syneos Health and Takeda. Invited speaker fees from Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Merck Sharp & Dohme, Merck Serono and Pfizer.

Dr Rebecca S Heist discloses: Consulting honoraria from Apollomics, Boehringer Ingelheim, Daichii Sankyo, EMD Serono, Novartis, and Takeda. Research funding (to institution, not to self) from Agios, AbbVie, Corvus, Daiichi Sankyo, Eli Lilly, Exelixis, Genentech Roche, Mirati, Novartis, and Turning Point.

Dr Takashi Seto discloses: Consulting honoraria from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Covidien Japan, Daiichi Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, Mochida Pharmaceutical, MSD, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical and Takeda Pharmaceutical. Research funding from Abbvie, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, LOXO Oncology, Merck Sharp & Dohme, Novartis Pharma, Pfizer Japan and Takeda Pharmaceutical.

Content reviewer

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

Touch Medical Director

Kathy Day 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: 29 July 2021. Date credits expire: 29 July 2022.

Learning Objectives

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

  • Recall the latest efficacy data from MET-inhibitor clinical trials in NSCLC
  • Describe diagnostic methods for the identification of MET exon 14 skipping mutations and MET amplification
  • Discuss practical adverse event management with MET inhibitors in the clinic
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Question 1/5
In the updated GEOMETRY mono-1 Cohort 7 data, presented at ASCO 2021, which patient subgroup showed the greatest efficacy outcomes with capmatinib?

ASCO, American Society of Clinical Oncology; MET, mesenchymal-epithelial transition; METex14, MET exon 14 skipping mutation; NSCLC, non-small cell lung cancer.
Correct

In GEOMETRY mono-1, patients (n=160) were assigned to cohorts based on previous lines of therapy and MET status (METex14 or MET amplification). Results of Cohort 7 showed a higher efficacy of capmatinib when used as first-line treatment in patients with METex14 NSCLC, with a similar median PFS to that previously reported for Cohort 5b (although not yet mature) and an ORR of 65.6%, which was greater than that reported for pre-treated patients (51.6% in second line and 40.6% in second- or third-line treatment) and similar to that previously reported for Cohort 5b.

MET, mesenchymal-epithelial transition; METex14, MET exon 14 skipping mutation; NSCLC, non-small cell lung cancer; ORR, overall response rate; PFS, progression-free survival.

Reference

Wolf J, et al. J Clin Oncol. 2021;39:suppl 15;abstr 9020.

Question 2/5
Data were presented at ASCO 2021 from the VISION Cohort B, in which 24 patients with MET amplification were prospectively detected by liquid biopsy and treated with tepotinib. In which treatment line was the highest overall response rate reported and may suggest higher efficacy in this patient subgroup?

ASCO, American Society of Clinical Oncology; MET, mesenchymal-epithelial transition.
Correct

VISION Cohort B evaluated tepotinib in 24 patients with advanced NSCLC and MET amplification, detected by liquid biopsy assay, in the absence of METex14. Tepotinib showed high and clinically meaningful activity, especially in the first line, with an ORR of 41.7% overall. In subgroup analyses, ORR by IRC was 71.4% in first line (n=7), 30.0% in second line (n=10) and 28.6% in third line (n=7).

IRC, independent review committee; MET, mesenchymal-epithelial transition; METex14, MET exon 14 skipping mutation; NSCLC, non-small cell lung cancer; ORR, objective response rate.

Reference

Le X, et al. J Clin Oncol. 2021;39:suppl 15;abstr 9021.

Question 3/5
Your patient is a 63-year-old man with advanced EGFR-mutant NSCLC who has received treatment with osimertinib. Mutational testing shows acquired MET amplification after progression. Based on data presented at ASCO 2021, what would be the preferred treatment regimen for this patient to overcome resistance?

ASCO, American Society of Clinical Oncology; EGFR, epidermal growth factor receptor; MET, mesenchymal-epithelial transition; METamp, MET amplification; NSCLC, non-small cell lung cancer; TKI, tyrosine kinase inhibitor.
Correct

Data presented at ASCO 2021 reported treatment with a combination approach that comprises simultaneous inhibition of EGFR and MET. A real-world study of crizotinib plus or minus EGFR-TKI in patients with acquired MET amplification post EGFR-TKI therapy reported greater efficacy with combination therapy versus monotherapy and versus chemotherapy.1 In addition, the use of amivantamab (an EGFR-MET bispecific antibody) plus lazertinib, an EGFR-TKI, yielded responses of 36% in patients who progressed on osimertinib.2

ASCO, American Society of Clinical Oncology; EGFR, epidermal growth factor receptor; MET, mesenchymal-epithelial transition; TKI, tyrosine kinase inhibitor.

References

  1.  Liu L et al. J Clin Oncol. 2021;39:suppl 15;abstr 9043
  2.  Bauml J, et al. J Clin Oncol. 2021;39:suppl 15;abstr 9006.
Question 4/5
Based on current research, which of the following would you select as the most accurate diagnostic testing approach for the identification of patients with METex14 skipping mutations?

FISH, fluorescent in situ hybridization; MET, mesenchymal-epithelial transition; METex14, MET exon 14 skipping mutation.
Correct

Historically, a number of different tests have been used to identify METex14 NSCLC, with NGS testing a rational choice.1 DNA-based sequencing alone may miss detection of the actionable genetic alteration, due to technical limitations in detecting gene rearrangements.1

Targeted RNA sequencing in addition to DNA sequencing can identify genomic rearrangements that are undetectable via DNA sequencing, providing lung adenocarcinoma patients with more opportunities for targeted therapy.1,2

Based on recent data presented at ASCO 2021, the authors concluded that the inclusion of RNA-sequencing should be recommended, particularly in patients where DNA-sequencing fails to detect a driver alteration.2

ASCO, American Society of Clinical Oncology; MET, mesenchymal-epithelial transition; METex14, MET exon 14 skipping mutation.

References

  1.  Socinski MA, et al. JCO Precision Oncol. 2021;5:653-63.
  2.  Zhao R et al. J Clin Oncol. 2021;39:suppl 15;abstr 3052.
Question 5/5
According to prescribing information, during treatment with both capmatinib and tepotinib in patients with METex14 NSCLC, when is it important to consider dose reduction?

MET, mesenchymal-epithelial transition; METex14, MET exon 14 skipping mutation; NSCLC, non-small cell lung cancer.
Correct

The FDA prescribing information for both tepotinib and capmatinib recommends that in the event of a grade 3 adverse event, the dose should be withheld until recovery, at which time MET-inhibitor treatment can be resumed at a reduced dose.1,2 Patients with severe hepatotoxicity, or any grade 4 adverse event, should permanently discontinue the selected MET inhibitor.

FDA, US Food and Drug Administration; MET, mesenchymal-epithelial transition.

References

  1.  Tepotinib Prescribing Information. 2020. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2021/214096s000lbl.pdf (accessed 5 May 2021).
  2.  Capmatinib Prescribing Information. 2020. Available at: www.accessdata.fda.gov/drugsatfda_docs/label/2020/213591s000lbl.pdf (accessed 5 May 2021).
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