Consensus or Controversy? Documenting and Discussing Investigators’ Approaches to the Management of Advanced Gastroesophageal Cancers — Symposium Proceedings

Faculty

TARGET AUDIENCE
This activity is intended for medical oncologists, hematologists, hematology-oncology fellows, radiation oncologists, surgeons and other allied healthcare professionals involved in the treatment of gastroesophageal tumors.

LEARNING OBJECTIVES

• Assess available data with claudin 18.2 (CLDN18.2)-directed monoclonal antibody therapy in combination with chemotherapy as first-line treatment for patients with HER2-negative, CLDN18.2-positive gastric or gastroesophageal junction (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 nonresearch role of various agents and regimens.
• Describe the published research data with anti-PD-1/PD-L1 antibodies alone or in combination with other systemic therapies in the management of metastatic gastric, GEJ and esophageal cancer, and optimally integrate these strategies into treatment algorithms.
• Recognize the spectrum, frequency and severity of toxicities associated with agents and regimens with established activity in advanced gastroesophageal cancers in order to facilitate the safe and effective use of these therapies.

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 1.75 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 this CME activity, which includes participation in the evaluation component and a post-test, enables the participant to earn up to 1.75 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 the 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, this program has been specifically designed for the following ABIM specialty: medical oncology.

AMERICAN BOARD OF SURGERY (ABS) — CONTINUOUS CERTIFICATION (CC)
Successful completion of this CME activity, 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, this program has 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 this activity, 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.

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 — Dr Shah has no relevant financial relationships to disclose. The following faculty reported relevant financial relationships with ineligible entities:

Prof Van Cutsem — 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.

CONTRIBUTING CLINICAL INVESTIGATORS
Sunnie Kim, MD — Advisory Committees: AstraZeneca Pharmaceuticals LP, BeOne, Takeda Pharmaceuticals USA Inc; Consulting Agreements: Amgen Inc; Contracted Research: Merck; Data and Safety Monitoring Boards/Committees: Jazz Pharmaceuticals Inc. Samuel J Klempner, MD — Advisory Committees: Astellas, AstraZeneca Pharmaceuticals LP, BeOne, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Daiichi Sankyo Inc, Eisai Inc, Elevation Oncology, EsoBiotec, Gilead Sciences Inc, I-Mab Biopharma, Jazz Pharmaceuticals Inc, Merck, Mersana Therapeutics Inc, Natera Inc, Novartis, Signet Therapeutics, Taiho Oncology Inc; Consulting Agreements: Astellas; Contracted Research: Arcus Biosciences, AstraZeneca Pharmaceuticals LP, I-Mab Biopharma, Mersana Therapeutics Inc, Parabilis Medicines; Data and Safety Monitoring Boards/Committees: Sanofi; Stock Options — Private Companies: MBrace Therapeutics; Nonrelevant Financial Relationships: Debbie’s Dream Foundation, Degregorio Family Foundation, Gastric Cancer Foundation, National Cancer Institute/National Institutes of Health, NCCN (member of Gastric and Esophageal Guidelines Committees), Stand Up 2 Cancer/AACR, Torrey Coast Foundation. Zev Wainberg, MD, MSc — 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 — Dr Janjigian — Advisory Committees: AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals Inc, Daiichi Sankyo Inc; Consulting Agreements: AbbVie Inc, AlphaSights, Arcus Biosciences, ARS Pharmaceuticals, AskGene Pharma, Astellas, AstraZeneca Pharmaceuticals LP, Basilea Pharmaceutica Ltd, Bayer HealthCare Pharmaceuticals, BeOne, Boehringer Ingelheim Pharmaceuticals Inc, Bristol Myers Squibb, Cencora, Daiichi Sankyo Inc, Eisai Inc, Geneos Therapeutics, Gilead Sciences Inc, GSK, Guardant Health, HC Wainwright & Co, Health Advances, Imugene, Inspirna, Lilly, Lynx Health, Merck, Merck Serono, Mersana Therapeutics Inc, PeerMD, Pfizer Inc, Sanofi, Seagen Inc, Suzhou Liangyihui Network Technology Co Ltd, Zymeworks Inc; Contracted Research: Arcus Biosciences, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Bristol Myers Squibb, Genentech, a member of the Roche Group, Inspirna, Lilly, Merck, Transcenta; Nonrelevant Financial Relationships: Clinical Care Options, Cycle for Survival, Debbie’s Dream Foundation, eChinaHealth, ED Medresources Inc, Fred’s Team, HMP, i3Health, Imedex, Mashup Media LLC, Master Clinician Alliance, MJH Life Sciences, National Cancer Institute, OncoDaily (stock options), Paradigm Medical Communications, PeerView, Physician Education Resource (PER), Stand Up 2 Cancer, Talem Health, TotalCME, US Department of Defense, WebMD.

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, Catalyst Pharmaceuticals Inc, 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, Tesaro, A GSK Company, and Verastem Inc.

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.

This educational activity contains 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.

This activity is supported by educational grants from Astellas and Jazz Pharmaceuticals Inc.

Release date: August 2026
Expiration date: August 2027

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

Prof Van Cutsem
Elimova E et al. Characterization and management of gastrointestinal (GI) adverse events (AEs) with zanidatamab + chemotherapy (CT) ± tislelizumab in first-line (1L) HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (mGEA): Analysis from HERIZON-GEA-01. ASCO 2026;Abstract 4042.

Janjigian YY et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: Interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet 2023;402(10418):2197-208. Abstract

Kawazoe A et al. KEYNOTE-811: 6-year median follow-up of pembrolizumab plus trastuzumab and chemotherapy for previously untreated advanced HER2-positive gastric or gastroesophageal junction adenocarcinoma. ASCO 2026;Abstract 4040.

Liu R et al. Anbenitamab in previously treated HER2-positive gastric cancer (KC-WISE): Prespecified interim analysis of a randomized, phase III clinical trial. Ann Oncol 2026;37(6):777-86. Abstract

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

Rha SY et al. Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced or metastatic gastroesophageal adenocarcinoma (mGEA): PD-L1 subgroup analysis from HERIZON-GEA-01. ASCO 2026;Abstract 4010.

Shitara K et al. Additional health-related quality of life (HRQoL) analysis from DESTINY-Gastric04 (DG-04), a randomized phase 3 study of trastuzumab deruxtecan (T-DXd) vs ramucirumab (RAM) + paclitaxel (PTX) in patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) unresectable/metastatic gastric cancer (GC)/gastroesophageal junction adenocarcinoma (GEJA). ASCO 2026;Abstract 4111.

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

Weisser NE et al. An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity. Nat Commun 2023;14(1):1394. Abstract

Dr Shah
Baek JH et al. Clinical implications of claudin18.2 expression in patients with gastric cancer. Anticancer Res 2019;39(12):6973-9. Abstract

Klempner SJ et al. Consensus guidance for prevention and management of nausea and vomiting in patients treated with zolbetuximab + chemotherapy: A RAND/UCLA modified Delphi panel study. ESMO Gastrointest Oncol 2025;7:100131. Abstract

Lordick F et al. Health-related quality of life in patients with CLDN18.2-positive, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma: Results from the SPOTLIGHT and GLOW clinical trials. ESMO Open 2024;9(8):103663. Abstract

Maeng CH et al. Clinicopathologic correlates of claudin 18.2 expression in esophagogastric cancer at multiple expression levels. ESMO Gastrointest Oncol 2026;11:100278. Abstract

Shitara K et al. Phase 2 ILUSTRO trial of 1L zolbetuximab plus mFOLFOX6 and nivolumab in patients with CLDN18.2+ locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Gastrointestinal Cancers Symposium 2026;Abstract LBA284.

Shitara K et al. Zolbetuximab + pembrolizumab and chemotherapy as first-line treatment for patients with CLDN18.2-positive, HER2-negative, PD-L1-positive locally advanced unresectable or metastatic G/GEJ adenocarcinoma: Phase 3, double-blind, randomized trial (LUCERNA). Gastrointestinal Cancers Symposium 2026;Abstract TPS473.

Shitara K et al. Zolbetuximab in gastric or gastroesophageal junction adenocarcinoma. N Engl J Med 2024;391(12):1159-62. Abstract

Dr Janjigian
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 treatment for advanced esophageal squamous cell carcinoma (ESCC): 5-year follow-up from CheckMate 648. ESMO 2025;Abstract 2106P.

Cruz-Correa M et al. Tislelizumab + chemotherapy in gastric cancer: Long-term RATIONALE-305 randomized trial follow-up. Adv Ther 2026;43(1):165-83. Abstract

Janjigian YY et al. Nivolumab plus chemotherapy as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 5-year follow-up results from CheckMate 649. Ann Oncol 2026;37(6):787-97. Abstract

Janjigian YY et al. First-line nivolumab plus chemotherapy for advanced gastric, gastroesophageal junction, and esophageal adenocarcinoma: 3-year follow-up of the phase III CheckMate 649 trial. J Clin Oncol 2024;42(17):2012-20. Abstract

Janjigian YY et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): A randomised, open-label, phase 3 trial. Lancet 2021;398(10294):27-40. Abstract

Janjigian YY et al. CheckMate-032 study: Efficacy and safety of nivolumab and nivolumab plus ipilimumab in patients with metastatic esophagogastric cancer. J Clin Oncol 2018;36(28):2836-44. Abstract

Metges J-P et al. Pembrolizumab plus chemotherapy versus chemotherapy for advanced esophageal cancer: 5-year extended follow-up for the randomized phase III KEYNOTE-590 study. ESMO Open 2025;10(12):105854. Abstract

Moehler MH et al. Rationale 305: Phase 3 study of tislelizumab plus chemotherapy vs placebo plus chemotherapy as first-line treatment (1L) of advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC). Gastrointestinal Cancers Symposium 2023;Abstract 286.

Oh D-Y et al. Nivolumab plus ipilimumab combined with chemotherapy as first-line treatment for HER2-negative unresectable advanced or recurrent gastric/gastroesophageal junction cancer: A randomized phase 3 trial (ATTRACTION-6). ASCO 2026;Abstract 4006.

Qiu M-Z et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial. BMJ 2024;385:e078876. Abstract

Rha SY et al. KEYNOTE-859: 4.5-year median follow-up of pembrolizumab plus chemotherapy for previously untreated advanced HER2-negative gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. ASCO 2025;Abstract 4036.

Rha SY et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): A multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol 2023;24(11):1181-95. Abstract

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.

Shah MA et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: The randomized, phase 3 GLOW trial. Nat Med 2023;29(8):2133-41. Abstract

Shitara K et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): A multicentre, randomised, double-blind, phase 3 trial. Lancet 2023;401(10389):1655-68. Abstract

Yoon HY et al. Tislelizumab (TIS) + chemotherapy (CT) vs placebo (PBO) + CT as first-line treatment for locally advanced (LA), unresectable esophageal squamous cell carcinoma (ESCC): PD-L1 tumor area positivity (TAP) score ≥1% subgroup analysis of RATIONALE-306. Gastrointestinal Cancers Symposium 2026;Abstract 381.