touchPANEL DISCUSSION

MET mutations: The next frontier in NSCLC testing

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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%

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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

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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

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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