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ASCO GI 2026 | Optimising first-line treatment in gastric cancer through precision medicine
Filippo Pietrantonio, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, highlights the importance of biomarker-driven first-line treatment selection in gastric cancer, including HER2, mismatch repair, PD-L1, and CLDN18.2 testing. Dr Pietrantonio explores emerging combination strategies with immunotherapy, monoclonal antibodies, and targeted agents, alongside the growing role of antibody-drug conjugates. Ongoing trials and novel mechanisms signal a promising and rapidly evolving treatment landscape for patients.This interview took place at the 2026 American Society of Clinical Oncology Gastrointestinal Cancers Symposium in San Francisco, CA.
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Transcript
As the discussants say today, so the first-line treatment choices are really impacting the most the disease scores. So choosing wisely in the first-line setting is of paramount importance and this is based on biomarker testing. So we know that the patients should undergo testing for R2 status, mismatch repair, PD-L1, and nowadays Claudin 18.2. So this is really crucial to select the best treatment option...
As the discussants say today, so the first-line treatment choices are really impacting the most the disease scores. So choosing wisely in the first-line setting is of paramount importance and this is based on biomarker testing. So we know that the patients should undergo testing for R2 status, mismatch repair, PD-L1, and nowadays Claudin 18.2. So this is really crucial to select the best treatment option. There are also other trials ongoing to really test whether, for example, the addition of zolbetuximab to chemoimmunotherapy regimens may further improve outcomes because of course there may be some overlapping between biomarkers. So as we already do for R2 positive disease by combining anti-R2 monoclonal antibodies with immunotherapy, the future for the treatment of gastric cancer may rely on combinations of monoclonal antibodies, immunotherapy and targeted agents. And hopefully in the future, we will be able to de-escalate even the chemotherapy intensity or shorten the duration of chemotherapy by the availability of effective targeted agent combinations. So I think the future is bright also because other agents are on the horizon. So, for example, ADCs are already a reality and trastuzumab deruxtecan is approved in the second-line setting and beyond, but it’s commonly used after trastuzumab first line therapy failure. And other ADCs are on the horizon. For example, Claudin 18.2 targeting ADCs may provide a good sequence starting from zolbetuximab and chemotherapy to Claudin 18.2 targeting ADCs in those tumors with high claudin DNA expression or positive expression. And TROP2 ADCs are also being investigated in phase 3 trials. And the novel agents such as B-specific monoclonal antibodies will be key to really bring novel mechanism of action in this difficult to treat disease. And so there is a lot going on in gastric cancer and this is good news for patients. Hopefully we will see other positive phase three practice change in trials, but from ASCO GI, I think that we saw a lot of interesting studies.
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