In advanced gastroesophageal cancer, a common clinical practice for patients achieving a complete response on immunotherapy is to stop treatment after two years. For those with residual disease confirmed by biopsy, clinicians advocate for extending therapy beyond this point, contingent on payer approval.

Some experts advocate for using immunotherapy in PD-L1 negative (CPS 0) gastric adenocarcinoma, arguing the biomarker test itself is unreliable. Factors like stromal sampling variability mean a "zero" score might not be truly negative, justifying treatment in a patient who would otherwise be excluded.

While median survival improvements in advanced HCC are notable, the truly revolutionary impact of immunotherapy is the creation of a long-term survival "tail" on the Kaplan-Meier curve. Clinicians now manage patients for years, a reality that was nonexistent in the pre-IO era.

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.

While neoadjuvant-only immunotherapy has a strong rationale, a patient-level cross-trial comparison of CheckMate 816 (neoadjuvant) and 770T (perioperative) suggests the addition of adjuvant therapy improves event-free survival, favoring a full perioperative approach.

The Matterhorn study found that adding the immunotherapy drug Durvalumab to FLOT chemotherapy significantly improved survival in localized gastric cancer. Surprisingly, this benefit extended to patients with low or negative PD-L1 expression, challenging the biomarker's predictive value for immunotherapy efficacy in this perioperative setting.

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.

The long-term separation of survival curves for zolbetuximab, a Claudin 18.2 antibody, suggests it does more than just target a protein. The "tail on the curve" effect is similar to that seen with immunotherapies, indicating that zolbetuximab may be activating a durable, sustained anti-tumor immune response.

In the increasingly common scenario of a patient with multiple positive biomarkers, a clear hierarchy exists for treatment decisions. Based on the robustness and maturity of clinical trial data, HER2-directed therapy is the top priority, followed by PD-L1 immunotherapy, with Claudin-18.2 targeting considered third.