When choosing between therapies for dually positive (Claudin+/PD-L1+) gastric cancer, the existence of robust five-year survival data for immunotherapy regimens provides a compelling reason to prioritize it over newer agents like zolbetuximab, which lack such long-term follow-up.

In the SPOTLIGHT trial, adding zolbituximab to FOLFOX for Claudin-18.2 positive patients improved progression-free and overall survival. However, it did not significantly increase the objective response rate, demonstrating that survival benefit can be decoupled from tumor shrinkage metrics.

If gastroesophageal cancer does not respond to first-line zolbetuximab, experts advise against continuing it with a new chemo backbone. This is based on tumor heterogeneity and parallels with a negative trial of continuing trastuzumab past progression in HER2+ disease.

Experts favor a Nivolumab plus Ipilimumab (NIVO+EP) combination for newly diagnosed, MSI-high, stage IV gastroesophageal cancer patients who can tolerate it. This approach avoids chemotherapy and yields high, sustained response rates, including potential for complete pathologic responses in metastatic settings.

New targeted therapies like Zanidatamab and Zolbetuximab show great promise but cause significant side effects like diarrhea and nausea. Their successful clinical adoption hinges on proactive management using detailed guidelines and prophylactic medications, as toxicity can be severe enough to force treatment discontinuation despite the drug's efficacy.

In the increasingly common scenario of gastric cancer with multiple biomarkers (HER2, PD-L1, Claudin), experts recommend a clear hierarchy. Based on data maturity, HER2-targeted therapy is the first choice, followed by PD-L1 immunotherapy, with Claudin-targeted therapy third.

New targeted therapies are often approved only for first-line use. This forces clinicians into a difficult choice: using one effective drug like a checkpoint inhibitor means forfeiting the chance to use another, like zolbetuximab, in a subsequent line of treatment, thereby losing a valuable therapeutic option.

When efficacy and safety profiles are comparable between ADCs like sacituzumab and datopotamab, the final choice can be guided by patient logistics. Factors include infusion frequency (Day 1 & 8 vs. every 3 weeks) and total time spent at the infusion center.

Severe nausea from the Claudin-18.2 antibody zolbetuximab dropped from ~20% in early trials to zero in a recent study. This was achieved not by changing the drug, but by clinicians learning and applying more effective proactive antiemetic strategies, demonstrating the power of evolving supportive care.