PD-L1 Cutoff for Pembrolizumab in Gastric Cancer

Treatment Recommendations

The National Comprehensive Cancer Network recommends pembrolizumab combined with fluoropyrimidine- and platinum-based chemotherapy for HER2-negative gastric cancer patients with a PD-L1 Combined Positive Score (CPS) ≥1, with CPS ≥5 representing the strongest evidence for benefit and Category 1 recommendation status 1
For HER2-positive gastric or GEJ adenocarcinoma, the National Comprehensive Cancer Network recommends pembrolizumab combined with trastuzumab and fluoropyrimidine/platinum chemotherapy, requiring CPS ≥1, as a Category 1 preferred first-line therapy option 1
The American Society of Clinical Oncology provides nuanced recommendations, including a strong recommendation for CPS ≥10 for esophageal/GEJ adenocarcinoma, and case-by-case consideration for CPS 1-10 5

The KEYNOTE-859 trial demonstrated a median overall survival of 15.7 months with pembrolizumab versus 11.8 months with placebo (HR 0.65, P <0.0001) in HER2-negative gastric/GEJ cancer patients with CPS ≥10 1
For CPS ≥1, the median overall survival was 13 months versus 11.4 months (HR 0.74, P <0.0001) in the KEYNOTE-859 trial 1

The National Comprehensive Cancer Network recommends PD-L1 testing using FDA-approved companion diagnostic assays in CLIA-approved laboratories, with a minimum requirement of at least 100 tumor cells for adequate evaluation 3
The FDA-approved assays (22C3 and SP263) show high concordance, with overall percent agreement >90% at CPS ≥1 and 99.2% at CPS ≥10 4

The National Comprehensive Cancer Network recommends testing all advanced gastric cancer for PD-L1 CPS using an FDA-approved assay, and treating based on HER2 status and PD-L1 CPS level 3
For MSI-H/dMMR gastric cancer, pembrolizumab monotherapy is approved regardless of PD-L1 status, with an objective response rate of 31% in the KEYNOTE-158 trial 1