Investigators Discuss the Optimal Management of HER2-Positive Gastrointestinal Cancers — Expert Second Opinion: Microlearning Activity 3

Faculty

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

LEARNING OBJECTIVES

• Review published and emerging research findings with human epidermal growth factor receptor 2 (HER2)-targeted therapies for patients with HER2-positive or HER2-low gastroesophageal cancers, and assess their current and future roles in treatment.
• Appreciate the clinical relevance of HER2 amplification or mutation for colorectal cancer, and consider the implications for biomarker assessment and clinical management.
• Evaluate published clinical trial findings with HER2-directed therapies for HER2-positive metastatic colorectal cancer, and optimally incorporate available agents into the clinical care of appropriately selected patients.

ACCREDITATION STATEMENT
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CREDIT DESIGNATION STATEMENT
Video Proceedings: Research To Practice 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.

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 0.5 (video) 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) — CONTINOUS 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, complete the post-test with a score of 80% or better and fill out the evaluation. Program location URLs are noted below:

Video Program: ResearchToPractice.com/ASCOGI26/HER2PosGI/Micro/3/Video and evaluation ResearchToPractice.com/ASCOGI26/HER2PosGI/Micro/3/Video/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 these activities. 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:

Haley Ellis, MD
Medical Oncologist 
Mass General Brigham Cancer Institute 
Harvard Medical School 
Boston, Massachusetts 

Advisory Committees: AstraZeneca Pharmaceuticals LP, Cogent Biosciences, Jazz Pharmaceuticals Inc; Honoraria: Incyte Corporation, Jazz Pharmaceuticals Inc; Nonrelevant Financial Relationships: Medscape, OncLive, The Jackson Laboratory.

Eric Van Cutsem, MD, PhD
Professor of Medicine
Digestive Oncology
University Hospitals Leuven
Leuven, Belgium

Consulting Agreements: AbbVie Inc, Agenus Inc, ALX Oncology, Amgen Inc, Arcus Biosciences, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, BeOne, BioNTech SE, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Cantargia, Daiichi Sankyo Inc, Debiopharm, Eisai Inc, ElmediX, Fosun Pharma, Galapagos NV, GSK, Incyte Corporation, Ipsen Biopharmaceuticals Inc, iTeos Therapeutics, Jazz Pharmaceuticals Inc, Johnson & Johnson, Lilly, Merck KGaA, Microbial Machines, Mirati Therapeutics Inc, MSD, Nordic Pharma, Novartis, Novocure Inc, Pfizer Inc, Pierre Fabre, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, Simcere, Taiho Oncology Inc, Takeda Pharmaceutical Company Limited, Trishula Therapeutics, Zymeworks Inc.

Zev Wainberg, MD, MSc
Co-Director, GI Oncology Program
Director of Early Phase Clinical Research
Jonsson Comprehensive Cancer Center
UCLA School of Medicine
Los Angeles, California

Consulting Agreements: AbbVie Inc, Amgen Inc, AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Daiichi Sankyo Inc, EMD Serono Inc, Gilead Sciences Inc, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Jazz Pharmaceuticals Inc, Lilly, Merck, Novartis, Novocure Inc, Pfizer Inc, Regeneron Pharmaceuticals Inc, Takeda Pharmaceuticals USA Inc; Contracted Research: Arcus Biosciences, Bristol Myers Squibb; Data and Safety Monitoring Boards/Committees: AstraZeneca Pharmaceuticals LP, Pfizer Inc.

MODERATOR
Lionel A Kankeu Fonkoua, MD
Senior Associate Consultant
Assistant Professor of Oncology
Division of Medical Oncology, GI Cancer Program
Mayo Clinic
Rochester, Minnesota

No relevant financial relationships to disclose.

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, Biotheranostics Inc, A Hologic Company, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Celcuity, 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, 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, Nuvation Bio Inc, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Revolution Medicines Inc, Rigel Pharmaceuticals Inc, R-Pharm US, Sanofi, Seagen Inc, Servier Pharmaceuticals LLC, SpringWorks Therapeutics Inc, Stemline Therapeutics Inc, Sumitomo Pharma America, Summit Therapeutics, 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 AstraZeneca Pharmaceuticals LP and Daiichi Sankyo Inc.

Release date: April 2026
Expiration date: April 2027

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

Dr Ellis

Ayasun R et al. The role of HER2 status in the biliary tract cancers. Cancers (Basel) 2023;15(9):2628. Abstract

Bartley AN et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: Guideline from the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology. J Clin Oncol 2017;35(4):446-44. Abstract

Harding JJ et al. Landmark analysis of overall survival (OS) by objective response in patients (pts) with previously treated, advanced HER2-positive biliary tract cancer (BTC): Post hoc analysis of the HERIZON-BTC-01 trial. Gastrointestinal Cancers Symposium 2026;Abstract 545.

Harding JJ et al. HERIZON-BTC-302: A phase 3 study of zanidatamab with standard-of-care (SOC) therapy vs SOC alone for first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced/metastatic biliary tract cancer (BTC). Gastrointestinal Cancers Symposium 2025;Abstract TPS648.

Ikeda M et al. Randomized, open-label, multicenter, phase III study of trastuzumab deruxtecan (T-DXd) with rilvegostomig vs standard of care (SOC) in first-line, human epidermal growth factor receptor 2 (HER2)-expressing, locally advanced or metastatic (LA/m) biliary tract cancer (BTC): DESTINY-BTC01. ESMO 2024;Abstract 261TiP.

Inoue K et al. Clinicomolecular profile and efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapy for HER2-amplified advanced biliary tract cancer. JCO Precis Oncol 2025:e2400718. Abstract

Kehmann L et al. Evolving therapeutic landscape of advanced biliary tract cancer: From chemotherapy to molecular targets. ESMO Open 2024;9(10):103706. Abstract

Lamarca A et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): A phase 3, open-label, randomised, controlled trial. Lancet Oncol 2021;22(5):690-701. Abstract

Lee C et al. Impact of HER2-positivity on prognosis and targeted therapeutic outcomes in advanced biliary tract cancer. Gastrointestinal Cancers Symposium 2025;Abstract 629.

Meric-Bernstam F et al. Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: Primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol 2024;42(1):47-58. Abstract

Oh D-Y et al. Durvalumab plus chemotherapy in advanced biliary tract cancer: 3-year overall survival update from the phase III TOPAZ-1 study. J Hepatol 2025;83(5):1092-101. Abstract

Ohba A et al. Trastuzumab deruxtecan in human epidermal growth factor receptor 2–expressing biliary tract cancer (HERB; NCCH1805): A multicenter, single-arm, phase II trial. J Clin Oncol 2024;42(27):3207-17. Abstract

Pant S et al. Zanidatamab in HER2-positive metastatic biliary tract cancer: Final results from HERIZON-BTC-01. JAMA Oncol 2025;12(1):106-9. Abstract

Søreide K et al. Biliary tract cancer. Eur J Surg Oncol 2025;51(6):108489. Abstract

Dr Wainberg

Cammarota A et al. Targeting HER2 in gastroesophageal cancer: A new appetite for an old plight. Drugs 2025;85(3):361-83. Abstract

Elimova E et al. Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma (mGEA): Primary analysis from HERIZON-GEA-01. Gastrointestinal Cancer Symposium 2026;Abstract LBA285.

Elimova E et al. Zanidatamab plus chemotherapy as first-line treatment for patients with HER2-positive advanced gastro-oesophageal adenocarcinoma: Primary results of a multicentre, single-arm, phase 2 study. Lancet Oncol 2025;26(7):847-59. Abstract

Janjigian YY et al. Final overall survival for the phase III, KEYNOTE-811 study of pembrolizumab plus trastuzumab and chemotherapy for HER2+ advanced, unresectable or metastatic G/GEJ adenocarcinoma. ESMO 2024;Abstract 1400O.

Janjigian YY et al. Trastuzumab deruxtecan (T-DXd) monotherapy and combinations in patients (pts) with advanced/metastatic HER2-positive (HER2+) esophageal, gastric or gastroesophageal junction adenocarcinoma (GEJA): DESTINY-Gastric03 (DG-03). ESMO 2024;Abstract 1401O.

Jubashi A et al. Prognostic and predictive factors for the efficacy and safety of trastuzumab deruxtecan in HER2-positive gastric or gastroesophageal junction cancer. Gastric Cancer 2025;28(1):63-73. Abstract

Klempner et al. ERBB2 copy number (CN) as a quantitative biomarker for real-world (RW) outcomes to anti-HER2 therapy in advanced gastroesophageal adenocarcinoma (adv GEA). ASCO 2021;Abstract 4045.

Shitara K et al. An open-label, randomized, multicenter, phase 3 study of trastuzumab deruxtecan (T-DXd) + chemotherapy (chemo) ± pembrolizumab (pembro) versus chemo + trastuzumab ± pembro in first-line metastatic HER2+ gastric or gastroesophageal junction (GEJ) cancer: DESTINY-Gastric05. ASCO 2025;Abstract TPS4207.

Shitara K et al. Trastuzumab deruxtecan or ramucirumab plus paclitaxel in gastric cancer. N Engl J Med 2025;393(4):336-48. Abstract

Shitara K et al. Trastuzumab deruxtecan in HER2-positive advanced gastric cancer: Exploratory biomarker analysis of the randomized, phase 2 DESTINY-Gastric01 trial. Nat Med 2024;30(7):1933-42. Abstract

Yamaguchi K et al. Trastuzumab deruxtecan in anti-human epidermal growth factor receptor 2 treatment-naive patients with human epidermal growth factor receptor 2-low gastric or gastroesophageal junction adenocarcinoma: Exploratory cohort results in a phase II trial. J Clin Oncol 2023;41(4):816-25. Abstract

Yang H et al. Oesophageal cancer. Lancet 2024;404(10466):1991-2005. Abstract

Prof Van Cutsem

Germani MM et al. Impact of human epidermal growth factor receptor 2 in patients with metastatic colorectal cancer treated with chemotherapy plus bevacizumab or anti-EGFRs: Exploratory analysis of eight randomized trials. J Clin Oncol 2025;43(29):3184-97. Abstract

Meric-Bernstam F et al. Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: A phase 1, dose-escalation and expansion study. Lancet Oncol 2022;23(12):1558-70. Abstract

Oh D-Y, Bang Y-J. HER2-targeted therapies – A role beyond breast cancer. Nat Rev Clin Oncol 2020;17(1):33-48. Abstract

Raghav K et al. Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): Primary results from a multicentre, randomised, phase 2 trial. Lancet Oncol 2024;25(9):1147-62. Abstract

Rha SY et al. Zanidatamab (Zani) + chemotherapy (CT) in first-line (1L) human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic colorectal cancer (mCRC). ESMO 2024;Abstract 516MO.

Sartore-Bianchi A et al. Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): A proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol 2016;17(6):738-46. Abstract

Strickler JH et al. MOUNTAINEER-03 phase III study design: First-line mFOLFOX6 + tucatinib + trastuzumab for HER2+ metastatic colorectal cancer. Future Oncol 2025;21(3):303-11. Abstract

Strickler JH et al. Final results of a phase 2 study of tucatinib and trastuzumab for HER2-positive mCRC (MOUNTAINEER). ASCO 2024;Abstract 3509.

Vaghi C et al. Targeting HER2 in metastatic colorectal cancer: Current therapies, biomarker refinement, and emerging strategies. Drugs 2026;86(1):37-57. Abstract

Yoshino T et al. Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer. Nat Commun 2023;14(1):3332. Abstract