touchPANEL DISCUSSION

MET mutations: The next frontier in NSCLC testing

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About This Activity

Activity Description and Learning Objectives

In this activity, experts in non-small cell lung cancer (NSCLC) discuss genetic testing for biomarkers including MET exon 14 skipping mutations.

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

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

Target Audience

This activity has been designed to meet the educational needs of practising oncology specialists, lung cancer specialists and respiratory healthcare professionals

Disclosures – Faculty

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.

Prof. Reckamp disclosures:
Fees for consultancy roles from Amgen, AstraZeneca, Boehringer Ingelheim, Calithera, Genentech, Lilly, Loxo, Takeda, and Tesaro.

Prof. Kerr disclosures:
Fees for consultancy roles from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Diaceutics, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Ventana. Speaker honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Medscape, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Prime Oncology, Roche, and Ventana.

Dr Paik disclosures:
Advisory Board fees from AbbVie, AstraZeneca, Boehringer Ingelheim, Calithera, Celgene, EMD Serono, and Lilly Oncology. Independent Data Monitoring Committee fees from Takeda.

Content Reviewer

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

Touch Medical Director

Martin Quinn, PhD, has no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

Oakstone Publishing designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit™. 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. A score of 70% or higher is needed to obtain CME credit. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

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 (AME). European physicians interested in converting AMA PRA Category 1 Credit™ into European CME credit (ECMEC) should contact the UEMS (www.uems.eu)

Date of original release: 12 August 2020. Date credits expire: 12 August 2021.

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Q1. According to the 2020 NCCN Guidelines for NSCLC, which biomarkers have FDA-approved targeted agents available and should therefore be tested?

  1. A. ALK, RET, HER2 and PD-L1
  2. B. ALK, ROS1, EGFR, PIK3CA and PD-L1
  3. C. ALK, ROS1, EGFR, BRAF, METex14 skipping mutations, RET and PD-L1
  4. D. METex14 skipping mutations only

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The 2020 NCCN guidelines for NSCLC recommend testing for ALK rearrangements, ROS1 rearrangements, EGFR mutations, BRAF mutations, MET exon 14 skipping mutations, RET rearrangements and PD-L1 expression levels because FDA-approved agents are available for these biomarkers.

Testing for other genetic variants may also be done – such as NTRK, MET amplification and HER2 mutations to identify these rare oncogenic driver variants for which effective therapy may be available, although there is less evidence to support testing.

Abbreviations
ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; FDA, US Food and Drug Administration; HER2, human epidermal growth factor receptor 2; METex14, mesenchymal–epithelial transition exon 14; NCCN, National Comprehensive Cancer Network; NSCLC, non-small-cell lung carcinoma; NTRK, neurotrophic tropomyosin receptor kinase; PD-L1, programmed death-ligand 1; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; RET, rearranged during transfection.

Reference
NCCN Guidelines (Non–Small Cell Lung Cancer, Version 6.2020). Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. (accessed June 2020)

Q2. Approximately what proportion of patients with NSCLC and the adenocarcinoma histologic subtype have METex14 skipping mutations?

  1. A. <1%
  2. B. 3% to 4%
  3. C. 8% to 12%
  4. D. 12% to 15%

Please try again

METex14 skipping mutations occur in 3–4% of patients with adenocarcinoma and 1–2% of patients with other NSCLC histologies. MET skipping mutations are more frequent in older women who are non-smokers.

Abbreviations
MET, mesenchymal–epithelial transition, NSCLC, non-small-cell lung carcinoma; NGS, next-generation sequencing; PCR, polymerase chain reaction.

Reference
NCCN Guidelines (Non–Small Cell Lung Cancer, Version 6.2020). Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (accessed June 2020)

Q3. Why might ctDNA testing (liquid biopsy) be especially helpful in identifying tumor mutations in NSCLC?

  1. A. It potentially bypasses tumor heterogeneity by including ctDNA from all tumor sites
  2. B. It requires a more invasive and time-consuming sample collection than tissue biopsy
  3. C. It is the historical standard of care for tumor sampling
  4. D. It has superior sensitivity and specificity to tissue biopsy

Please try again

In NSCLC tumor biomarker testing, liquid biopsy is noninvasive and easily repeatable over time, and captures systemic tumor burden, which may be more complete than single-site sampling that may be affected by tumor heterogeneity.1,2

Tissue biopsy is the historical standard for biomarker identification, and has higher sensitivity, but serial sample collection can be too burdensome for the patient to be feasible.1,2

Abbreviations
ctDNA, circulating tumor DNA; NSCLC, non-small-cell lung carcinoma

References

  1. Pennell NA, et al. Am Soc Clin Oncol Educ Book. 2019;39:531–542
  2. Rolfo C, et al. J Thorac Oncol. 2018;13:1248–1268.

Q4. In which clinical circumstances would you specifically consider using ctDNA testing (liquid biopsy) in NSCLC?

  1. A. At all stages of diagnosis and treatment, even when tissue biopsy is feasible
  2. B. Only after progression with at least 2 lines of therapy
  3. C. Never - ctDNA has no value in NSCLC
  4. D. As an alternative method when tissue biopsy specimens are insufficient or unfeasible

Please try again

NCCN guidelines state that ctDNA testing should not be used in lieu of histologic tissue diagnosis. ctDNA generally has a very high specificity, but low sensitivity with up to 30% false-negative rate. In addition, standards for analytical performance for ctDNA have not yet been established.1

Liquid biopsy offers an alternative to standard procedures when tissue biopsy specimens are insufficient or unfeasible.2

Abbreviations
ctDNA, circulating tumor DNA; NSCLC, non-small-cell lung carcinoma

References

  1. NCCN Guidelines (Non–Small Cell Lung Cancer, Version 6.2020). Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (accessed June 2020)
  2. Rolfo C, et al. J Thorac Oncol. 2018;13:1248–1268.
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touchPANEL DISCUSSION

MET mutations: The next frontier in NSCLC testing

Introduction

Watch a panel of internationally recognized experts discuss genetic testing for lung cancer biomarkers including MET exon 14 skipping mutations

Professor Karen Reckamp chairs a discussion with Professor Keith Kerr and Dr Paul K. Paik on testing approaches for MET exon 14 skipping mutations, and the evolution of genetic testing methods in NSCLC

This activity is intended for practising oncology specialists, lung cancer specialists and respiratory HCPs

This touchPANEL DISCUSSION was recorded in July 2020.

Learning Objectives

After watching this touchPANEL DISCUSSION, you should be able to:

  • Recall relevant guidelines recommendations on the type and timing of mutation testing in patients with NSCLC
  • Discuss the current role of liquid biopsy in NSCLC mutation testing and treatment decisions
  • Discuss the developing contributions of tissue and liquid biopsy to clinical practice, as well as broader NGS-based assays

Clinical Spotlight

  • Update on practical guideline recommendations for biomarker testing in NSCLC.
  • How should liquid biopsy be used to identify genetic mutations in NSCLC? Focus on the clinical application of liquid biopsy and tissue biopsy for therapeutic decision-making.
  • What is the role of comprehensive genomic profiling using NGS to help make treatment recommendations? Discussing the evolution of genetic testing.

Clinical Spotlight

  • Update on practical guideline recommendations for biomarker testing in NSCLC.
  • How should liquid biopsy be used to identify genetic mutations in NSCLC? Focus on the clinical application of liquid biopsy and tissue biopsy for therapeutic decision-making.
  • What is the role of comprehensive genomic profiling using NGS to help make treatment recommendations? Discussing the evolution of genetic testing.

The Expert Panel

PROF.
KAREN RECKAMP

PROF.
KEITH KERR

DR
PAUL K. PAIK

PROF. KAREN RECKAMP

Karen L. Reckamp, MD, MS is Professor in Medicine, Director of the Division of Medical Oncology at Cedars-Sinai Medical Center, and serves as the Associate Director of Clinical Research for the Samuel Oschin Comprehensive Cancer Institute (SOCCI). She leads several Phase I, II and III studies funded by the National Cancer Institute (NCI), Institutions, and Industry, and has led the American Society of Clinical Oncology (ASCO) Annual Meeting Scientific Committee for metastatic lung cancer.

Disclosures:

Fees for consultancy roles from Amgen, AstraZeneca, Boehringer Ingelheim, Calithera, Genentech, Lilly, Loxo, Takeda, and Tesaro.

PROF. KEITH KERR

Keith Kerr is a Consultant Pathologist for NHS Grampian and Honorary Chair in Pulmonary Pathology at the University of Aberdeen in Scotland, Chair of the IASLC Pathology Panel and served on the IASLC Board of Directors from 2013 to 2017. He has a busy diagnostic clinical practice and is active in lung cancer research. He has worked on numerous clinical research lung cancer trials groups, guideline panels, and conference scientific committees.

Disclosures:

Fees for consultancy roles from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Diaceutics, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Ventana. Speaker honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Medscape, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Prime Oncology, Roche, and Ventana.

DR PAUL K. PAIK

Paul K. Paik, MD is a medical oncologist at Memorial Sloan Kettering Cancer Center (MSKCC) who specializes in the treatment of lung cancers. He is an Associate Attending Physician in the Thoracic Oncology Service at MSKCC, an Associate Professor of Medicine at Weill Cornell Medical College, and serves as the Clinical Director for the Thoracic Oncology Program at MSKCC. His research focuses on squamous cell lung cancer, targeted therapeutics, and translational therapies aimed at the metastatic process.

Disclosures:

Advisory Board fees from AbbVie, AstraZeneca, Boehringer Ingelheim, Calithera, Celgene, EMD Serono, and Lilly Oncology. Independent Data Monitoring Committee fees from Takeda.

About This Activity

Activity Description and Learning Objectives

In this activity, experts in non-small cell lung cancer (NSCLC) discuss genetic testing for biomarkers including MET exon 14 skipping mutations.

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

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

  • Recall relevant guidelines recommendations on the type and timing of mutation testing in patients with NSCLC
  • Discuss the current role of liquid biopsy in NSCLC mutation testing and treatment decisions
  • Discuss the developing contributions of tissue and liquid biopsy to clinical practice, as well as broader next-generation sequencing (NGS)-based assays

Target Audience

This activity has been designed to meet the educational needs of practising oncology specialists, lung cancer specialists and respiratory healthcare professionals

Disclosures – Faculty

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.

Prof. Reckamp disclosures:
Fees for consultancy roles from Amgen, AstraZeneca, Boehringer Ingelheim, Calithera, Genentech, Lilly, Loxo, Takeda, and Tesaro.

Prof. Kerr disclosures:
Fees for consultancy roles from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Diaceutics, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Ventana. Speaker honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Medscape, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Prime Oncology, Roche, and Ventana.

Dr Paik disclosures:
Advisory Board fees from AbbVie, AstraZeneca, Boehringer Ingelheim, Calithera, Celgene, EMD Serono, and Lilly Oncology. Independent Data Monitoring Committee fees from Takeda.

Content Reviewer

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

Touch Medical Director

Martin Quinn, PhD, has no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

Oakstone Publishing designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit™. 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. A score of 70% or higher is needed to obtain CME credit. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

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 (AME). European physicians interested in converting AMA PRA Category 1 Credit™ into European CME credit (ECMEC) should contact the UEMS (www.uems.eu)

Date of original release: 12 August 2020. Date credits expire: 12 August 2021.