Current and Future Management of HER2-Altered Non-Small Cell Lung Cancer — Video Lecture

Faculty

John V Heymach

MD, PhD

The University of Texas MD Anderson Cancer Center, Houston, Texas

Professor and Chair, Thoracic/Head and Neck Medical Oncology

TARGET AUDIENCE
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of lung cancer.

LEARNING OBJECTIVES

• Appreciate the incidence and clinical relevance of human epidermal growth factor receptor 2 (HER2) mutations and protein overexpression in non-small cell lung cancer (NSCLC) and consider the implications for biomarker assessment and current clinical management.
• Evaluate published research findings and current guideline recommendations to individualize the selection and sequencing of therapy for patients with HER2-mutant NSCLC.
• Review available clinical trial data evaluating the efficacy and safety of HER2-targeted tyrosine kinase inhibitors (TKIs) in patients with HER2-mutant NSCLC in preparation for the potential clinical availability of this therapeutic strategy.
• Appraise the biological rationale for and available efficacy and safety findings with HER2-directed antibody-drug conjugates for HER2-overexpressing NSCLC and assess the optimal placement of this form of therapy in current treatment algorithms.
• Recognize the spectrum, frequency, severity and optimal management of toxicities associated with HER2-targeted TKIs and antibody-drug conjugates with established activity in lung cancer to facilitate the safe and effective current or future use of these agents.
• Assess available efficacy and safety data and ongoing clinical trials with novel HER2-targeted agents and combination regimens in lung cancer, and counsel appropriate patients about availability and participation.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
Video Interview: Research To Practice designates this enduring material for a maximum of 1.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Video Lecture: Research To Practice designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the participant to earn up to 1.25 (video) and 0.75 (lecture) Medical Knowledge MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for each activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

Please note, these programs have been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINUOUS CERTIFICATION (CC)
Successful completion of these CME activities, which includes participation in the evaluation components and post-tests, enables the learner to earn credit toward the CME and Self-Assessment requirement(s) of the American Board of Surgery’s Continuous Certification program. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABS credit.

Please note, these programs have been specifically designed for the following ABS practice area: complex general surgical oncology.

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HOW TO USE THIS CME ACTIVITY
To receive credit for an activity in this series, the participant should review the CME information, listen to or view the MP3s, review the downloadable slide set, complete the post-test with a score of 80% or better and fill out the evaluation. Program location URLs are noted below:

Video Interview: ResearchToPractice.com/OncologyTodayHERAlteredNSCLC25/Video and evaluation ResearchToPractice.com/OncologyTodayHERAlteredNSCLC25/Video/CME.

Video Lecture: ResearchToPractice.com/OncologyTodayHERAlteredNSCLC25/Presentation and evaluation ResearchToPractice.com/OncologyTodayHERAlteredNSCLC25/Presentation/CME.

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education and adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education. Any individuals in a position to control the content of an accredited continuing education activity, including faculty, planners, reviewers and others, are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant financial relationships have been mitigated prior to the commencement of this activity. In addition, all activity content is reviewed by RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty reported relevant financial relationships with ineligible entities:

John V Heymach, MD, PhD
Professor and Chair
Thoracic/Head and Neck Medical Oncology
The University of Texas MD Anderson Cancer Center
Houston, Texas

Advisory Committees: AbbVie Inc, AnHeart Therapeutics, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, BioAtla, BioNTech SE, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Dizal, Ellipses Pharma, EMD Serono Inc, Genentech, a member of the Roche Group, GSK, Hengrui Therapeutics Inc, Johnson & Johnson, Leads Biolabs, Lilly, ModeX Therapeutics, Novartis, Pfizer Inc, Regeneron Pharmaceuticals Inc, Sanofi, Spectrum Pharmaceuticals Inc, Takeda Pharmaceuticals USA Inc, United Therapeutics Corporation; Research Support: AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Spectrum Pharmaceuticals Inc, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc; Royalties and Licensing Fees: Spectrum Pharmaceuticals Inc.

EDITOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following companies: Aadi Bioscience, AbbVie Inc, ADC Therapeutics, Agendia Inc, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeOne, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Clovis Oncology, Coherus BioSciences, Corcept Therapeutics Inc, CTI BioPharma, a Sobi Company, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology Inc, Exact Sciences Corporation, Exelixis Inc, Genentech, a member of the Roche Group, Genmab US Inc, Geron Corporation, Gilead Sciences Inc, GSK, Helsinn Therapeutics (US) Inc, Hologic Inc, ImmunoGen Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Johnson & Johnson, Karyopharm Therapeutics, Kite, A Gilead Company, Kura Oncology, Legend Biotech, Lilly, MEI Pharma Inc, Merck, Mersana Therapeutics Inc, Mirati Therapeutics Inc, Mural Oncology Inc, Natera Inc, Novartis, Novartis Pharmaceuticals Corporation on behalf of Advanced Accelerator Applications, Novocure Inc, Nuvalent, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Sumitomo Pharma America, Syndax Pharmaceuticals, Taiho Oncology Inc, Takeda Pharmaceuticals USA Inc, TerSera Therapeutics LLC, and Tesaro, A GSK Company. 

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant financial relationships to disclose.

These educational activities contain discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

These activities are supported by educational grants from Bayer HealthCare Pharmaceuticals and Boehringer Ingelheim Pharmaceuticals Inc.

Release date: November 2025
Expiration date: November 2026

After completing the post-test, learners may download and review the answers here in order to identify further areas of study.

Goto K et al. Trastuzumab deruxtecan in patients with HER2-mutant metastatic non-small-cell lung cancer: Primary results from the randomized, phase II DESTINY-Lung02 trial. J Clin Oncol 2023;41(31):4852-63. Abstract

Heymach JV et al. HER2-selective tyrosine kinase inhibitor, zongertinib (BI 1810631), in patients with advanced/metastatic solid tumors with HER2 alterations: A phase Ia dose-escalation study. J Clin Oncol 2025;43(11):1337-47. Abstract

Heymach JV et al. Zongertinib in patients with pretreated HER2-mutant advanced NSCLC: Beamion LUNG-1. AACR 2025;Abstract CT050.

Heymach JV et al. Zongertinib in previously treated HER2-mutant non-small-cell lung cancer. N Engl J Med 2025;392(23):2321-33. Abstract

Johnson ML et al. Beamion LUNG-2: A phase III randomized controlled trial of zongertinib (BI 1810631) versus standard of care (SoC) in patients with locally advanced/metastatic non-squamous non-small cell lung cancer (NSCLC) harboring HER2 tyrosine kinase domain (TKD) mutations. ASCO 2024;Abstract TPS8654.

Le X et al. Sevabertinib (BAY 2927088) in advanced HER2-mutant non-small cell lung cancer (NSCLC): Results from the SOHO-01 study. ESMO 2025;Abstract LBA75.

Le X et al. SOHO-02: Phase III trial of BAY 2927088 in patients with locally advanced or metastatic NSCLC with HER2-activating mutations. ASCO 2025;Abstract TPS8648.

Nilsson MB et al. Trastuzumab deruxtecan resistance can be mediated by payload resistance or secondary extracellular ERBB2 mutations but sensitivity to HER2 tyrosine kinase inhibitors is maintained. AACR 2024;Abstract 5857.

Popat S et al. Zongertinib as first-line treatment in patients with advanced HER2-mutant NSCLC: Beamion LUNG 1. ESMO 2025;Abstract LBA74.

Wilding B et al. Zongertinib (BI 1810631), an irreversible HER2 TKI, spares EGFR signaling and improves therapeutic response in preclinical models and patients with HER2-driven cancers. Cancer Discov 2025;15(1):119-38. Abstract