FDA Considers Restricting PD-1 Drugs in Stomach and Esophageal Cancers Based on PD-L1 Expression

FDA Review:
The FDA's Oncologic Drugs Advisory Committee (ODAC) recently discussed the use of PD-1 drugs in stomach and esophageal cancers, focusing on whether PD-L1 expression should be a criterion for patient selection.

Current Approvals:
Pembrolizumab is currently approved for use in HER2-positive gastric/GEJ adenocarcinoma only in patients with PD-L1 combined positive score (CPS) ≥1, based on the KEYNOTE-811 trial.

European Approvals:
The European Medicines Agency (EMA) has approved pembrolizumab for gastric/GEJ adenocarcinoma with PD-L1 CPS ≥1 and nivolumab for CPS ≥5%.

Clinical Trials:
Studies like KEYNOTE-811 and CHECKMATE-649 have shown that PD-L1 expression is a predictive biomarker for the effectiveness of PD-1 drugs in gastric cancer.

Risk-Benefit Assessment:
The FDA is evaluating whether the benefits of PD-1 drugs in patients with low or no PD-L1 expression outweigh the risks, considering that some trials suggest potential harm in these subpopulations.

Future Directions:
The discussion aims to refine the indications for PD-1 drugs in stomach and esophageal cancers to better match patients with treatments likely to provide benefit, potentially leading to revised approvals based on PD-L1 expression levels.