Clinical Investigators Review Actual Cases of Patients with HER2-Positive Gastrointestinal Cancers

Faculty

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

LEARNING OBJECTIVES

• Appreciate the prevalence and clinical relevance of HER2 amplification/overexpression in various gastrointestinal (GI) cancers, and consider the implications for biomarker assessment and clinical management.
• Evaluate available clinical trial findings with HER2-directed therapies for HER2-positive biliary tract cancers, and optimally incorporate available agents into the care of appropriately selected patients.
• Review published research findings with established and investigational HER2-targeted therapies for patients with HER2-positive gastroesophageal cancers, and assess the current and future role of various agents and regimens.
• Recall available data with HER2-targeted agents and strategies for previously treated HER2-overexpressing colorectal cancer, and optimally identify patients who may be appropriate for these approaches.
• Appraise the side effects associated with available and investigational HER2-directed therapies with established efficacy in GI cancers, and use this information to develop supportive care plans for patients.
• Recall the design of ongoing clinical trials evaluating novel HER2-directed agents and strategies for advanced HER2-positive GI cancers, and appropriately counsel 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 Program: 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.

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) 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..

PRIVACY POLICY
Personal information and data sharing: Research To Practice aggregates deidentified user data for program-use analysis, program development, activity planning and site improvement. We may provide aggregate and deidentified data to third parties, including commercial supporters. We do not share or sell personally identifiable information to any unaffiliated third parties or commercial supporters. Please see our privacy policy at ResearchToPractice.com/Privacy-Policy for more information.

HOW TO USE THIS CME ACTIVITY
Video Program: This CME activity consists of a video component. To receive credit, the participant should review the CME information, watch the video, complete the post-test with a score of 80% or better and fill out the evaluation located at ResearchToPractice.com/PP2025/HER2PosGI/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 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:

Tanios Bekaii-Saab, MD
David F and Margaret T Grohne Professor of Novel Therapeutics
for Cancer Research I
Chair and Consultant, Division of Hematology and Medical Oncology
Co-Leader, Advanced Clinical and Translational Science Program
Mayo Clinic Comprehensive Cancer Center (All Sites)
Professor, Mayo Clinic College of Medicine and Science
Mayo Clinic in Arizona
Phoenix, Arizona

Consulting Agreements (to Institution): Arcus Biosciences, Bayer HealthCare Pharmaceuticals, Eisai Inc, Genentech, a member of the Roche Group, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Merck, Merck KGaA, Merus, Pfizer Inc, Revolution Medicines, Seagen Inc, Servier Pharmaceuticals LLC; Consulting Agreements (to Self): AbbVie Inc, Aptitude Health, AstraZeneca Pharmaceuticals LP, BeOne, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Celularity, Daiichi Sankyo Inc, Deciphera Pharmaceuticals Inc, Exact Sciences Corporation, Exelixis Inc, Foundation Medicine, GSK, Illumina, Janssen Biotech Inc, Kanaph Therapeutics, Lisata Therapeutics, Natera Inc, Sanofi, Sobi, Stemline Therapeutics Inc, Takeda Pharmaceuticals USA Inc, Treos Bio, Xilio Therapeutics, Zai Lab; Data and Safety Monitoring Boards/Committees: 1Globe Health Institute, AstraZeneca Pharmaceuticals LP, Eisai Inc, Exelixis Inc, FibroGen Inc, Merck, Suzhou Kintor; Inventions/Patents: WO/2018/183488 licensed to Imugene, WO/2019/055687 licensed to Recursion; Research Funding (to Institution): Agios Pharmaceuticals Inc, AltruBio, Arcus Biosciences, Arrys Therapeutics, a wholly owned subsidiary of Kyn Therapeutics, Atreca, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, Celgene Corporation, Eisai Inc, Genentech, a member of the Roche Group, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Lilly, Merus, Mirati Therapeutics Inc, Novartis, Pfizer Inc, pharmaand GmbH, Seagen Inc, Sumitomo Pharma America; Scientific Advisory Boards: Artiva Biotherapeutics Inc, Immuneering Corporation, Imugene, Panbela Therapeutics Inc, Replimune, Xilis; Nonrelevant Financial Relationships: MJH Life Sciences, Pancreatic Cancer Action Network, The Valley Hospital.

Kristen K Ciombor, MD, MSCI
Associate Professor of Medicine
Division of Hematology/Oncology
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee

Advisory Committees and Consulting Agreements: Agenus Inc, ALX Oncology, Bayer HealthCare Pharmaceuticals, BeOne, Exact Sciences Corporation, Exelixis Inc, Incyte Corporation, Merck, Pfizer Inc, Summit Therapeutics, Taiho Oncology Inc, Tempus; Contracted Research: Array BioPharma Inc, a subsidiary of Pfizer Inc, Biomea Fusion Inc, Bristol Myers Squibb, Calithera Biosciences, Genentech, a member of the Roche Group, Incyte Corporation, Merck, NuCana, Pfizer Inc, Seagen Inc, Syndax Pharmaceuticals; Data and Safety Monitoring Boards/Committees: AstraZeneca Pharmaceuticals LP.

MODERATOR — 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 grantor.

These activities are supported by an educational grant from Jazz 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.

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

Bekaii-Saab TS et al. MOUNTAINEER-03: Phase 3 study of tucatinib, trastuzumab, and modified FOLFOX6 as first line treatment in HER2+ metastatic colorectal cancer. ASCO 2023;Abstract TPS3631.

Catenacci DVT et al. MOUNTAINEER-02: Phase 2/3 study of tucatinib, trastuzumab, ramucirumab, and paclitaxel in previously treated HER2+ gastric or gastroesophageal junction adenocarcinoma — Trial in progress. Gastrointestinal Cancers Symposium 2022;Abstract TPS371.

Elimova E et al. Long-term outcomes and overall survival (OS) for zanidatamab + chemotherapy in HER2-positive (HER2+) advanced or metastatic gastroesophageal adenocarcinoma (mGEA): 4-year follow-up of a phase 2 trial. ASCO 2025;Abstract 4013.

Galdy S et al. HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: A potential therapeutic target? Cancer Metastasis Rev 2017;36(1):141-57. Abstract

Geyer CE et al. Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients with high-risk human epidermal growth factor receptor 2–positive (HER2+) primary breast cancer (BC) with residual invasive disease after neoadjuvant therapy (tx): Interim analysis of DESTINY-Breast05. ESMO 2025;Abstract LBA1.

Harbeck N et al. DESTINY-Breast11: Neoadjuvant trastuzumab deruxtecan alone (T-DXd) or followed by paclitaxel + trastuzumab + pertuzumab (T-DXd-THP) vs SOC for high-risk HER2+ early breast cancer (eBC). ESMO 2025;Abstract 291O.

Harding J 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.

Jacobi O et al. ERBB2 pathway in biliary tract carcinoma: Clinical implications of a targetable pathway. Oncol Res Treat 2021;44(1-2):20-7. Abstract

Javle M et al. Biliary cancer: Utility of next-generation sequencing for clinical management. Cancer 2016;15;122(24):3838-47. Abstract

Kanwal W et al. Exploring zanidatamab’s efficacy across HER2-positive malignancies: A narrative review. BMC Cancer 2025;25(1):382. 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

Lee K-W et al. A 2-year follow-up of zanidatamab (Zani) + mFOLFOX6 ± bevacizumab (Bev) in first-line (1L) treatment of patients with human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic colorectal cancer (mCRC). ESMO 2025;Abstract 746P.

Mercade TM et al. HERIZON-BTC-302: A phase III study of zanidatamab with standard-of-care (SOC) therapy vs SOC alone for first-line (1L) treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced/metastatic biliary tract cancer (BTC). ESMO 2024;Abstract 62TiP.

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

Meric-Bernstam F et al. Efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing solid tumors: DESTINY-PanTumor02 (DP-02) interim results. ASCO 2023;Abstract LBA3000.

Pant S et al. Zanidatamab in previously-treated HER2-positive (HER2+) biliary tract cancer (BTC): Overall survival (OS) and longer follow-up from the phase 2b HERIZON-BTC-01 study. ASCO 2024;Abstract 4091.

Raghav KPS et al. Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-overexpressing/amplified (HER2+) metastatic colorectal cancer (mCRC): Primary results from the multicenter, randomized, phase 2 DESTINY-CRC02 study. ASCO 2023;Abstract 3501.

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.

Shitara K et al. Trastuzumab deruxtecan (T-DXd) vs ramucirumab (RAM) + paclitaxel (PTX) in second-line treatment of patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) unresectable/metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJA): Primary analysis of the randomized, phase 3 DESTINY-Gastric04 study. ASCO 2025;Abstract LBA4002.

Søreide K et al; joint ESSO-EAHPBA-UEMS core curriculum working group. Biliary tract cancer. Eur J Surg Oncol 2025;51(6):108489. 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.

Subbiah V et al. DiscovHER PAN-206: Phase II tumour-agnostic study of zanidatamab in patients with previously treated human epidermal growth factor receptor 2 (HER2)-overexpressing solid tumours. ESMO 2025;Abstract 1028eTiP.

Tabernero J et al. HERIZON-GEA-01: Zanidatamab + chemo ± tislelizumab for 1L treatment of HER2-positive gastroesophageal adenocarcinoma. Future Oncol 2022;18(29):3255-66. Abstract

Uzunparmak B et al. HER2-low expression in patients with advanced or metastatic solid tumors. Ann Oncol 2023;34(11):1035-46. Abstract