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    Faculty & Disclosures
    Prof. Paul Paik

    Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Prof. Paul Paik, MD, is a medical oncologist at the Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, USA, who specializes in the treatment of lung cancers. read more

    He is an associate attending physician at 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. Prof. Paik’s research focuses on squamous cell lung cancer, targeted therapeutics and translational therapies aimed at the metastatic process.

    Prof. Paul Paik discloses: Advisory board or panel fees from Bicara Therapeutics (relationship terminated), EMD Serono, Janssen Pharmaceuticals (relationship terminated), Mirati Therapeutics (relationship terminated) and Takeda (relationship terminated). Consultancy fees from Novartis (relationship terminated). Grants/research support from Bicara Therapeutics, EMD Serono and Genentech.
    Dr Yasushi Goto

    National Cancer Center Hospital, Tokyo, Japan

    Dr Yasushi Goto, MD, PhD, is the assistant chief in the Division of Thoracic Oncology at the National Cancer Center Hospital in Tokyo, Japan. He received his medical and doctorate degree from the University of Tokyo. read more

    Dr Goto’s current research focus is in medical oncology (thoracic malignancies) and translational medicine. He is an author on more than 50 scientific papers, including publications in the Journal of Thoracic Oncology, Journal of Clinical Oncology, The Lancet and New England Journal of Medicine. He is a member of steering committees for several global and domestic studies, and a primary investigator of the Japan Clinical Oncology Group trial. He is a member of the Japanese Society of Internal Medicine, the Japanese Respiratory Society, the Japanese Cancer Association, the Japan Lung Cancer Society, the Japanese Society of Medical Oncology, the American Society of Clinical Oncology, the European Society of Medical Oncology, and the International Association for the Study of Lung Cancer.

    Dr Yasushi Goto discloses: Consultancy fees from AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, GSK, Guardant Health, Illumina, Janssen Pharmaceuticals, Kyorin Pharmaceutical, Merck, MSD, Novartis, Ono Pharmaceutical, Pfizer and Taiho Pharmaceutical. Grants/research support from Abbvie, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Guardant Health, Kyorin Pharmaceutical, MSD, Novartis, Ono Pharmaceutical, Pfizer and Preferred Network. Speakers’ bureau fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Guardant Health, Kyowa Kirin, Merck, MSD, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Takeda, Thermo Fisher Scientific and Towa Pharmaceutical.
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    Part One
    Evolving landscape of biomarker testing in advanced NSCLC
    Identifying METex14 skipping mutations in NSCLC
    Targeting METex14 skipping mutations in advanced NSCLC
    Part Two
    Emerging mechanisms of resistance to EGFR-TKI therapy in advanced NSCLC
    Targeting MET amplification in advanced NSCLC
    Optimizing outcomes for patients with MET alterations in advanced NSCLC
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    Lung Cancer CE/CME accredited

    touchIN CONVERSATION
    A relaxed discussion between two faculty focussed on real world clinical issues. Useful tips below will show how to navigate the activity. Join the conversation. Close

    Personalized therapy for NSCLC: Biomarker testing, treatment and management in the presence of MET alterations

    Faculty Podcast Featured
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    • Select in the video player controls bar to choose subtitle language. Subtitles available in English, Japanese.
    • Downloads including slides are available for this activity in the Toolkit
    Learning Objectives

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

    • Outline the evolving landscape of biomarker testing in advanced NSCLC and the methods used to identify patients with MET alterations
    • Recall the latest efficacy and safety from MET-inhibitor clinical trials in advanced NSCLC and implications for management
    • Discuss the mechanisms of resistance to targeted treatment in advanced NSCLC and the role of MET amplification as a potential therapeutic target in the post EGFR-TKI setting
    Overview

    In this activity, Prof. Paul Paik and Dr Yasushi Goto discuss the current biomarker recommendations for NSCLC and the evolving treatment landscape in the management of patients with MET alterations. They consider biomarker tests used to guide first-line treatment, the current evidence for MET inhibitors, and how to optimize their use in patients with NSCLC. The discussion is guided by pre-canvassed questions provided by the lung cancer clinical community.

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

    Target Audience

    Oncologists including lung cancer specialists, respiratory specialists and pathology specialists involved in the management of NSCLC.

    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

    Prof. Paul Paik discloses: Advisory board or panel fees from Bicara Therapeutics (relationship terminated), EMD Serono, Janssen Pharmaceuticals (relationship terminated), Mirati Therapeutics (relationship terminated) and Takeda (relationship terminated). Consultancy fees from Novartis (relationship terminated). Grants/research support from Bicara Therapeutics, EMD Serono and Genentech.

    Dr Yasushi Goto discloses: Consultancy fees from AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, GSK, Guardant Health, Illumina, Janssen Pharmaceuticals, Kyorin Pharmaceutical, Merck, MSD, Novartis, Ono Pharmaceutical, Pfizer and Taiho Pharmaceutical. Grants/research support from Abbvie, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Guardant Health, Kyorin Pharmaceutical, MSD, Novartis, Ono Pharmaceutical, Pfizer and Preferred Network. Speakers’ bureau fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly, Guardant Health, Kyowa Kirin, Merck, MSD, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Takeda, Thermo Fisher Scientific and Towa Pharmaceutical.

    Content Reviewer

    Alicia Canalejo has no financial interests/relationships or affiliations in relation to this activity.

    Touch Medical Contributors

    Kathy Day has 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: 14 September 2023. Date credits expire: 5 October 2024.

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

    This activity is CE/CME accredited

    To obtain the CE/CME credit(s) from this activity, please complete this post-activity test.

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    • Select in the video player controls bar to choose subtitle language. Subtitles available in English, Japanese.
    • Downloads including slides are available for this activity in the Toolkit

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    This Activity Is Funded By:

    An independent medical education grant from the healthcare business of Merck KGaA, Darmstadt, Germany, and 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: 14 September 2023. Date credits expire: 5 October 2024.

     

    Claim Credit
    touchIN CONVERSATION
    Personalized therapy for NSCLC: Biomarker testing, treatment and management in the presence of MET alterations
    0.75 CE/CME credit
    Question 1/5
    When discussing molecular testing for your patient with newly diagnosed stage IV NSCLC, which testing methodology would you recommend, assuming all testing methods are available to you to detect a broad range of molecular alterations, including METex14 skipping mutations?

    METex14, mesenchymal-epithelial transition exon 14; NSCLC, non-small cell lung cancer; PCR, polymerase chain reaction.

    Although immunohistochemistry is able to detect MET overexpression in patients with NSCLC, its utility for predicting the presence of METex14 alterations is poor. One of the main weaknesses of PCR-based assays is that knowledge of the fusion partner is required for primer design, which can be challenging when detecting novel fusions. Sanger sequencing has been shown to have a high specificity but a lower sensitivity than next-generation sequencing. Next-generation sequencing can analyse multiple regions of multiple genes.

    Abbreviations

    METex14, mesenchymal-epithelial transition exon 14; NSCLC, non-small cell lung cancer; PCR, polymerase chain reaction.

    Reference

    Tan AC, et al. Lung Cancer (Auckl). 2021;12:11–20.

    Question 2/5
    You are treating a 71-year-old female patient with metastatic NSCLC who has not received prior systemic chemotherapy. Molecular testing revealed a positive result for METex14 skipping mutations. What first-line approach would you select based on the current NCCN guidelines?

    METex14, mesenchymal-epithelial transition exon 14; NCCN, National Comprehensive Cancer Network; NSCLC, non-small cell lung cancer.

    The NCCN guidelines recommend that patients with advanced or metastatic NSCLC, who test positive for METex14 skipping mutation prior to first-line systemic therapy, receive capmatinib or tepotinib as the preferred first-line treatment option.1 Guidelines in most Asian countries encourage recruitment into open trials for patients with METex14 skipping mutations.2

    Abbreviations

    METex14, mesenchymal-epithelial transition exon 14; NCCN, National Comprehensive Cancer Network; NSCLC, non-small cell lung cancer.

    References

    1. NCCN. Non-small cell lung cancer. V3.2023. Available at: bit.ly/3JsD9K2 (accessed 19 July 2023).
    2. Wu YL, et al. Ann Oncol. 2019;30:171–210.
    Question 3/5
    Your patient with METex14 skipping mutation–positive metastatic NSCLC is about to start treatment with the MET inhibitor, tepotinib. What is the best approach to address the potential adverse event of peripheral oedema?

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

    Treatment-related peripheral oedema is a common adverse event, occurring in 63% of patients with METex14-mutated NSCLC treated with tepotinib.1 Although time to onset has been reported from approximately 8 weeks with tepotinib, management strategies for peripheral oedema include early and vigilant monitoring from initiation of treatment, as well as prophylactic measures, such as support stockings, bed elevation, reduction in dietary salt intake, lymphoedema massage, and continuing daily activities.2 Diuretics may be transiently effective.2 

    Abbreviations

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

    References

    1. Paik P, et al. N Engl J Med. 2020;383:931–43.
    2. Cortot A, et al. Clin Lung Cancer. 2022;23:195–207.
    Question 4/5
    Which is the most common EGFR-independent mechanism of acquired resistance in patients with NSCLC who are refractory to treatment with the third-generation EGFR-TKI, osimertinib?

    EGFR, epidermal growth factor receptor; NSCLC, non-small cell lung cancer; TKI, tyrosine kinase inhibitor.

    MET amplification is considered a pivotal EGFR-independent resistance mechanism, estimated to occur in 5–24% of disease progression following osimertinib use in any line of therapy. Another EGFR-independent mechanism is HER2 amplification, which occurs in 2% of patients who develop resistance to first-line osimertinib and 5% of patients who develop resistance to second-line osimertinib. C797S mutation is the most common EGFR-dependent resistance mechanism to osimertinib, reported to occur between 11% and 29% of patients in real-world cohorts. While T790M mutation occurs in a high proportion of patients treated with first- or second-generation EGFR-TKIs, the significance of T790M mutation does not usually exist when osimertinib is used upfront.

    Abbreviations

    EGFR, epidermal growth factor receptor; HER2, human epidermal growth factor receptor 2; MET, mesenchymal-epithelial transition; TKI, tyrosine kinase inhibitor. 

    Reference

    Gomatou G, et al. Cancers (Basel). 2023;15:841.

    Question 5/5
    You are managing a patient with EGFR-mutant NSCLC who is refractory to first-line treatment with the third-generation EGFR-TKI, osimertinib. He tests positive for MET amplification and you suggest a clinical trial. Following discussion, in which of the following would you enrol your patient based on the latest evidence?

    ADC, antibody–drug conjugate; EGFR, epidermal growth factor receptor; MET, mesenchymal-epithelial transition; NSCLC, non-small cell lung cancer; TKI, tyrosine kinase inhibitor.

    Currently, MET inhibitors are not approved for use for patients with MET amplification following prior treatment with EGFR-TKI. However, promising results have been shown in a number of phase I/II studies investigating the use of an EGFR-TKI plus MET inhibitor to overcome MET-amplification-mediated resistance to EGFR-TKIs in EGFR-mutated NSCLC.

    Abbreviations

    EGFR, epidermal growth factor receptor; MET, mesenchymal-epithelial transition; NSCLC, non-small cell lung cancer; TKI, tyrosine kinase inhibitor. 

    Reference

    Quin K, et al. Cancers. 2023;15:612.

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    This Activity Is Funded By:

    An independent medical education grant from the healthcare business of Merck KGaA, Darmstadt, Germany, and 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: 14 September 2023. Date credits expire: 5 October 2024.

     

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