Clinical Investigators Discuss the Current and Future Clinical Care of Patients with HER2-Positive Gastrointestinal Cancers — Symposium Video Proceedings

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 relevance of HER2 amplification and overexpression in various 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 recently approved agents into the care of appropriately selected patients.
• Review published research findings with established HER2-targeted therapies for patients with HER2-positive gastroesophageal cancers, and assess the current role of various agents and regimens outside of a research setting.
• Recall available data with HER2-targeted agents and strategies for previously treated HER2-overexpressing colorectal cancer, and optimally identify patients for whom these approaches may be appropriate.
• Understand the biological rationale for and available clinical trial findings with novel HER2-directed bispecific antibodies for patients with HER2-positive GI cancers, and contemplate the current and potential utility of these agents in the management of various diseases.
• Appraise the side effects associated with available HER2-directed therapies with established efficacy for GI cancers, and use this information to develop supportive care plans for patients undergoing treatment with these agents or regimens.
• Recall the design of ongoing clinical trials evaluating 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 1.75 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 component and a post-test, enables the participant to earn up to 1.75 (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 component and a post-test, 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
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/ASCO2025/HER2GI/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:

Haley Ellis, MD
Medical Oncologist
Massachusetts General Hospital
Instructor of Medicine
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.

Sara Lonardi, MD
Director of the Oncology 1 Unit
Veneto Institute of Oncology IOV-IRCCS
Padua, Italy

No relevant financial relationships to disclose.

Kanwal Raghav, MD, MBBS
Associate Professor, Gastrointestinal Medical Oncology
Associate Vice President (AVP), Ambulatory Medical Operations
Executive Medical Director (EMD), Ambulatory Treatment Centers
The University of Texas MD Anderson Cancer Center
Houston, Texas

Advisory Committees and Contracted Research: AbbVie Inc, AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Eisai Inc, Guardant Health, Janssen Biotech Inc, Merck, Pfizer Inc; Data and Safety Monitoring Boards/Committees: AbbVie Inc, Pfizer Inc.

MODERATOR
Christopher Lieu, MD
Professor of Medicine
Associate Director for Clinical Research
Co-Director, GI Medical Oncology
University of Colorado Cancer Center
Aurora, Colorado

Consulting Agreements (to Institution): Pfizer Inc; Contracted Research (All to Institution): Genentech, a member of the Roche Group, Janssen Biotech Inc, Sanofi.

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, Daiichi Sankyo Inc, and Jazz Pharmaceuticals Inc.

Release date: June 2025
Expiration date: June 2026

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

Dr Lonardi

Cancer Genome Atlas Network. Integrated genomic characterization of oesophageal carcinoma. Nature 2017;541(7636):169-75. Abstract

Elimova E et al. Zanidatamab + chemotherapy for first-line (1L) treatment of HER2+ advanced or metastatic gastro-oesophageal adenocarcinoma (mGEA): New and updated data from a phase II trial. ESMO 2024;Abstract 1423P.

Fassan M et al. Current prognostic and predictive biomarkers for gastrointestinal tumors in clinical practice. Pathologica 2020;112(3):248-59. 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.

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.

Shitara K et al. Negative hyperselection of patients with RAS wild-type metastatic colorectal cancer for panitumumab: A biomarker study of the phase III PARADIGM trial. Gastrointestinal Cancers Symposium 2022;Abstract 11.

Shitara K et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med 2020;382(25):2419-30. Abstract

Van Cutsem E et al. Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02): Primary and updated analyses from a single-arm, phase 2 study. Lancet Oncol 2023;24(7):744-56. Abstract

Wilke H et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): A double-blind, randomised phase 3 trial. Lancet Oncol 2014;15(11):1224-35. Abstract

Yamaguchi K et al. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2–positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: Final overall survival (OS) results from a randomized, multicenter, open-label, phase 2 study (DESTINY-Gastric01). Gastrointestinal Cancers Symposium 2022;Abstract 242.

Zhao D et al. Progress and challenges in HER2-positive gastroesophageal adenocarcinoma. J Hematol Oncol 2019;12(1):50. Abstract

 

Dr Ellis

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.

Harding JJ et al. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): A multicentre, single-arm, phase 2b study. Lancet Oncol 2023;24(7):772-82. Abstract

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.

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

Kehmann L et al. Evolving therapeutic landscape of advanced biliary tract cancer: From chemotherapy to molecular targets. ESMO Open 2024;9(10). 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-K 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;[Online ahead of print]. Abstract

Oh D-Y et al. Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-expressing biliary tract cancer (BTC) and pancreatic cancer (PC): Outcomes from DESTINY-PanTumor02 (DP-02). ASCO 2024;Abstract 4090.

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 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.

Søreide K et al. Pancreatic cancer. Eur J Surg Oncol 2023;49(2):521-5. Abstract

 

Dr Raghav

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

Raghav KPS et al. Trastuzumab plus pertuzumab versus cetuximab plus irinotecan in patients with RAS/BRAF wild-type, HER2-positive, metastatic colorectal cancer (S1613): A randomized phase II trial. J Clin Oncol 2025;43(11):1348-57. Abstract

Raghav KPS 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

Raghav KPS, Moasser MM. Molecular pathways and mechanisms of HER2 in cancer therapy. Clin Cancer Res 2023;29(13):2351-61. Abstract

Rha SY et al. EDGE-Gastric arm A1: Phase II study of domvanalimab (D), zimberelimab (Z), and FOLFOX in first-line (1L) advanced gastroesophageal (GE) cancer. ESMO 2024;Abstract 130MO.

Siena S et al. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): A multicentre, open-label, phase 2 trial. Lancet Oncol 2021;22(6):779-89. 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.

Strickler JH et al. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): A multicentre, open-label, phase 2 study. Lancet Oncol 2023;24(5):496-508. Abstract