FDA Questions PD-1 Cancer Drugs for Gastric Cancer Patients

On September 26, the FDA's Oncologic Drugs Advisory Committee will evaluate the use of immune checkpoint inhibitors for patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma, as well as esophageal squamous cell carcinoma. The current approvals for these drugs are broad, not considering the varying levels of programmed death cell ligand-1 (PD-L1) expression among patients. Cumulative data suggests that PD-L1 expression may serve as a predictive biomarker for treatment efficacy, but clinical trials have employed different methods and thresholds for determining PD-L1 positivity. The FDA's review includes existing approvals for drugs such as Opdivo (nivolumab) and Keytruda (pembrolizumab), along with pending applications for Tevimbra (tislelizumab). The agency's briefing document indicates that combining immune checkpoint inhibitors with standard chemotherapy does not provide benefits for patients with PD-L1 expression below 1%. In contrast, patients with PD-L1 levels of 10% or higher show significant treatment benefits. The effectiveness of treatment for patients with PD-L1 levels between 1% and 10% remains uncertain, complicating data interpretation. The FDA has expressed concerns that patients with low or absent PD-L1 expression are unlikely to gain benefits from anti-PD-1 therapy, which may instead introduce risks such as severe immune-related adverse effects. These risks could further impact the quality of life for patients already battling cancer. The advisory committee's discussions may lead to a reevaluation of the current labeling for PD-1 inhibitors, potentially limiting their use in gastric cancer patients based on PD-L1 expression levels. This could significantly affect treatment options and strategies for managing this patient population moving forward.