Experts Review Actual Cases of Patients with Advanced Gastroesophageal Cancers — Part 1 of 2 — Webinar 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 gastroesophageal cancers.

LEARNING OBJECTIVES

• Understand validated biomarkers of response, such as HER2 overexpression, PD-L1 combined positive score and claudin 18.2 (CLDN18.2) expression, found in patients with gastric, gastroesophageal junction (GEJ) and esophageal cancers, and consider the implications for molecular testing and clinical care.
• Describe the published research data with anti-PD-1/PD-L1 antibodies alone or in combination with other systemic therapies in the management metastatic gastric, GEJ and esophageal cancers, and optimally integrate these strategies into nonresearch treatment algorithms.
• Assess available data with monoclonal antibody therapy directed at CLDN18.2 in combination with chemotherapy as first-line treatment for patients with HER2-negative, CLDN18.2-positive gastric or GEJ cancer, and optimally incorporate this approach into management algorithms.
• Review published research findings with HER2-targeted therapies for patients with HER2-positive gastroesophageal cancers, and assess the current and potential roles of various agents and regimens in the care of appropriately selected patients.
• Review the rationale for, available data with and ongoing research studies evaluating novel agents and strategies for patients with gastroesophageal cancers in preparation for potential clinical availability or to enhance trial 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
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 component and a post-test, 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) — 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/PPGI2025/4/AdvancedGE/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:

Geoffrey Y Ku, MD
Associate Attending Physician
Head, Esophagogastric Section
Gastrointestinal Oncology Service
Member, Cellular Therapy Service
Department of Medicine
Memorial Sloan Kettering Cancer Center
New York, New York

Advisory Committees and Consulting Agreements: Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, Daiichi Sankyo Inc, I-Mab Biopharma, Jazz Pharmaceuticals Inc, Merck, Oncolys BioPharma, Pieris Pharmaceuticals Inc, Zymeworks Inc; Contracted Research: AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb, CARsgen Therapeutics, Daiichi Sankyo Inc, I-Mab Biopharma, Jazz Pharmaceuticals Inc, Merck, Oncolys BioPharma, Pieris Pharmaceuticals Inc, Triumvira Immunologics, Zymeworks Inc; Travel Support: DAVA Oncology, I-Mab Biopharma.

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, Alligator Bioscience, Amgen Inc, Arcus Biosciences, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, BridgeBio, Daiichi Sankyo Inc, EMD Serono Inc, Genentech, a member of the Roche Group, Incyte Corporation, Ipsen Biopharmaceuticals Inc, Lilly, Merck, Novartis, Phanes Therapeutics Inc; Data and Safety Monitoring Boards/Committees: AstraZeneca Pharmaceuticals LP, Compass Therapeutics, Pfizer Inc.

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, Alexion Pharmaceuticals, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Arvinas, Astellas, AstraZeneca Pharmaceuticals LP, Aveo Pharmaceuticals, Bayer HealthCare Pharmaceuticals, BeiGene Ltd, Black Diamond Therapeutics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Clovis Oncology, Coherus BioSciences, 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, 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, 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, Bristol Myers Squibb, Jazz Pharmaceuticals Inc, and Merck.

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.

Catenacci D 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.

Chao J et al. Assessment of pembrolizumab therapy for the treatment of microsatellite instability-high gastric or gastroesophageal junction cancer among patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 clinical trials. JAMA Oncol 2021;7(6):895-902. Abstract

Chau I et al. Nivolumab (NIVO) plus chemotherapy (chemo) or ipilimumab (IPI) vs chemo as first-line (1L) treatment for advanced esophageal squamous cell carcinoma (ESCC): 45-month (mo) follow-up from CheckMate 648. ASCO 2024;Abstract 4034.

Elimova E et al. Nivolumab (NIVO) + chemotherapy (chemo) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): 4-year follow-up of CheckMate 649. ASCO 2024;Abstract 4040.

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.

Janjigian YY et al. CLARITY-Gastric 01: A randomized phase 3 study of AZD0901, a Claudin18.2 (CLDN18.2)-targeted antibody-drug conjugate, in second- or later-line (2L+) advanced gastric or gastroesophageal junction cancer (GC/GEJC). Gastrointestinal Cancers Symposium 2025;Abstract TPS507.

Janjigian YY et al. Nivolumab (NIVO) + chemotherapy (chemo) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): 5-year (y) follow-up results from CheckMate 649. Gastrointestinal Cancers Symposium 2025;Abstract 398.

Janjigian YY et al. Updated results from the trastuzumab deruxtecan (T-DXd) 5.4 mg/kg triplet combination of DESTINY-Gastric03 (DG-03): First-line (1L) T-DXd with fluoropyrimidine (FP) and pembrolizumab in advanced/metastatic HER2-positive (HER2+) esophageal adenocarcinoma, gastric cancer (GC), or gastroesophageal junction adenocarcinoma (GEJA). Gastrointestinal Cancers Symposium 2025;Abstract 448.

Janjigian YY et al. Pathological complete response (pCR) to 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) with or without durvalumab (D) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Subgroup analysis by region from the phase 3, randomized, double-blind MATTERHORN study. Gastrointestinal Cancers Symposium 2024;Abstract LBA246.

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

Ku GY et al. Updated analysis of DESTINY-Gastric02: A phase II single-arm trial of trastuzumab deruxtecan (T-DXd) in western patients (pts) with HER2-positive (HER2+) unresectable/metastatic gastric/gastroesophageal junction (GEJ) cancer who progressed on or after trastuzumab-containing regimen. ESMO 2022;Abstract 1205MO.

Lordick F et al. Updated efficacy and safety results from phase III GLOW study evaluating zolbetuximab + CAPOX as first-line (1L) treatment for patients with claudin-18 isoform 2-positive (CLDN18.2+), HER2−, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. ESMO 2024;Abstract 134MO.

Rha SY 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 128MO.

Shah MA et al. First-line pembrolizumab (pembro) plus chemotherapy (chemo) for advanced esophageal cancer: 5-year outcomes from the phase 3 KEYNOTE-590 study. Gastrointestinal Cancers Symposium 2024;Abstract 250.

Shitara K et al. Final overall survival results from phase 3 SPOTLIGHT study evaluating zolbetuximab + mFOLFOX6 as first-line (1L) treatment for patients (pts) with claudin 18 isoform 2 (CLDN18.2)+, HER2−, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. ASCO 2024;Abstract 4036.

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

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;24:744-56. Abstract

Xu R-H et al. A phase 1 trial of claudin 18.2-specific antibody-drug conjugate CMG901 in patients with advanced gastric/gastroesophageal junction cancer. ASCO 2024;Abstract 434420.

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.

Yoon HH et al. Global, randomized, phase III study of tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced/metastatic esophageal squamous cell carcinoma (RATIONALE-306 update): Minimum 3-year survival follow-up. ASCO 2024;Abstract 4032.