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Advances in the management of metastatic gastric cancer: current strategies and emerging therapeutics

Nature Reviews Clinical Oncology (2026)Cite this article

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Abstract

Metastatic gastric cancer remains a major global health challenge with poor long-term outcomes. Over the past 5 years, the treatment landscape has rapidly evolved with the integration of biomarker-informed strategies that guide the use of immune checkpoint inhibitors and targeted therapies in molecularly defined subgroups, including microsatellite unstable, PD-L1-expressing, HER2-positive and claudin 18.2-positive disease. Standard first-line treatment continues to rely on fluoropyrimidine–platinum chemotherapy backbones, with biomarker-driven agents selectively layered on for improved efficacy. Despite these advances, most patients continue to have disease progression, and durable responses are uncommon. In addition to identifying and validating new targets such as FGFR2b, ongoing efforts are focusing on novel strategies involving established targets, including HER2 and claudin 18.2, using next-generation treatment modalities such as antibody–drug conjugates, bispecific antibodies and cellular therapies. Complementary platforms including circulating tumour DNA and theranostic agents are also being explored to better guide treatment selection, facilitate non-invasive monitoring and enable early response assessments. In this Review, we summarize the current standard of care for patients with metastatic gastric cancer and also highlight emerging approaches aimed at improving the outcomes in these patients.

Key points

  • The treatment landscape of metastatic gastric cancer has undergone a progressive shift towards biomarker-informed strategies, with therapeutic benefit concentrated in molecularly defined subgroups of patients.

  • Fluoropyrimidine–platinum chemotherapy remains the backbone of first-line therapy, with incremental improvements achieved through the selective biomarker-guided addition of immune checkpoint inhibitors and/or targeted agents.

  • A high risk of both primary and acquired resistance to current first-line therapies exists, indicating a need to move beyond first-generation antibodies towards next-generation modalities, including antibody–drug conjugates, bispecific antibodies and cellular therapies.

  • Incorporation of dynamic, minimally invasive platforms such as circulating tumour DNA and theranostics has the potential to improve patient selection, enable real-time disease monitoring and support more adaptive treatment strategies.

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Fig. 1: Outcomes of key global randomized trials testing first-line chemo-immunotherapy regimens.
Fig. 2: First-line treatment selection in patients with advanced-stage gastric or GEJ cancers.
Fig. 3: Selected targeted and tumour microenvironment-modulating therapies in patients with advanced-stage gastric or GEJ cancer.

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Authors and Affiliations

  1. Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, NY, USA

    Joan Choo & Yelena Janjigian

  2. Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore

    Joan Choo

  3. Yeolyan Oncology and Hematology Center, Yerevan, Armenia

    Amalya Sargsyan

  4. Department of Internal Medicine, Flushing Hospital Medical Center, New York, NY, USA

    Vahe Khachatryan

  5. Department of Oncology, Veneto Institute of Oncology IRCCS, Padova, Italy

    Sara Lonardi

  6. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Filippo Pietrantonio

  7. Department of Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA

    Raghav Sundar

  8. Department of Medicine, Division of Hematology-Oncology, Massachusetts General Hospital, Boston, MA, USA

    Samuel Klempner

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  1. Joan Choo
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  2. Amalya Sargsyan
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Contributions

J.C., A.S. and V.K. researched data for the article, J.C., A.S., V.K., F.P., R.S., S.K. and Y.J. made a substantial contribution to discussion of content, J.C., A.S., V.K. and Y.J. wrote the manuscript, and all authors reviewed and/or edited the manuscript prior to submission.

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Correspondence to Yelena Janjigian.

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F.P. has acted as a consultant and/or adviser to Agenus, Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Daiichi Sankyo, Gilead, GSK, Incyte, Italfarmaco, Jazz Pharmaceuticals, Johnson & Johnson, Merck-Serono, MSD, Pfizer, Pierre-Fabre, Revolution Medicines, Rottapharm, Servier and Takeda; has received institutional research grants from Agenus, Amgen, AstraZeneca, BMS, GSK, Incyte, Johnson & Johnson, Lilly and Rottapharm; and has acted as an invited speaker for Amgen, Astellas, AstraZeneca, Bayer, BeOne, BMS, Daiichi Sankyo, Incyte, Ipsen, Johnson & Johnson, Merck-Serono, MSD, Pierre-Fabre, Seagen, Servier and Takeda. R.S. has acted as an adviser of Astellas, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Daiichi Sankyo, DKSH, Eisai, GSK, Merck, MSD, Novartis, Pierre-Fabre, Sanofi, Taiho and Tavotek BioTherapeutics; has acted as an invited speaker for Astellas, AstraZeneca, BeiGene, BMS, Daiichi Sankyo, DKSH, Eli Lilly, Ipsen, MSD, Roche and Taiho; has received travel support from AstraZeneca, CytoMed, DKSH, Eisai, Ipsen, Paxman, Roche and Taiho; has received research funding from MSD, Natera and Paxman Coolers; declares stock ownership of Teladoc; and is listed on patents pending, which are licensed to Paxman and in the processing of being licensed to Auristone. S.K. has acted as a consultant and/or adviser to Astellas, AstraZeneca, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Elevation Oncology, EsoBiotec, Gilead, I-Mab, Merck, Mersana, Natera, Novartis and Taiho; has received research support from AACR, Arcus Biosciences, AstraZeneca, Debbie’s Dream Foundation, the Degregorio Foundation, the Gastric Cancer Foundation, I-Mab, Mersana, NIH/NCI, Parabilis, Stand Up 2 Cancer and the Torrey Coast Foundation; and has acted as an uncompensated adviser for the NCCN guidelines for gastric and oesophageal cancers and to the medical advisory board for Debbie’s Dream Foundation. Y.J. has acted as an adviser and/or consultant to Abbvie, Alphasights, Amerisource Bergen, Ask-Gene Pharma, Inc., Arcus Biosciences, Astellas, Astra Zeneca, Basilea Pharmaceutica, Bayer, BeOne, Boehringer Ingelheim, Bristol Myers Squibb, Clinical Care Options, Daiichi Sankyo, Debbie’s Dream Foundation, eChina Health, Ed Med Resources (OncInfo), Eisai, Eli Lilly, Geneos Therapeutics, Gilead Sciences, GlaxoSmithKline, Guardant Health, Inc., H.C. Wainwright & Co., Health Advances, HMP Global, Imedex, Imugene, Inspirna, LLC, Lynx Health, Mashup Media LLC, Master Clinician Alliance, Merck, Merck Serono, Mersana Therapeutics, Michael J. Hennessy Associates, Oncology News, Paradigm Medical Communications, PeerMD, PeerView Institute, Pfizer, Physician’s Education Resource, Research to Practice, Sanofi Genzyme, Seagen, Silverback Therapeutics, Suzhou Liangyihui Network Technology Co., Ltd, Talem Health, TotalCME, WebMD and Zymeworks Inc; has received research funding from Astellas, AstraZeneca, Arcus Biosciences, Bayer, Bristol Myers Squibb, Cycle for Survival, Department of Defense, Eli Lilly, Fred’s Team, Genentech/Roche, Inspirna, Merck, NCI, Stand Up 2 Cancer and Transcenta; and holds stock options in Inspirna and Veda Life Sciences. The other authors declare no competing interests.

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Nature Reviews Clinical Oncology thanks Maria Alsina, Florian Lordick, Kohei Shitara and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Choo, J., Sargsyan, A., Khachatryan, V. et al. Advances in the management of metastatic gastric cancer: current strategies and emerging therapeutics. Nat Rev Clin Oncol (2026). https://doi.org/10.1038/s41571-026-01134-1

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