A New Treatment Option for Advanced Gastric Cancer?

Adding immune checkpoint inhibitors to first-line chemotherapy for patients with metastatic gastric cancer improves response, progression-free survival (PFS) and overall survival (OS). The benefit is limited to patients testing positive for a combined score for PDL-1.

Investigators now report the results of a multinational, industry-sponsored, placebo-controlled randomized trial comparing investigators' choice of first-line chemotherapy (capecitabine/oxaliplatin or infusional 5-FU/cisplatin) with versus without the addition of the anti–PD-1 agent tislelizumab (200 mg every 3 weeks). Of the 997 patients enrolled, 75% were treated in Asia, 38% had liver metastases, 44% had peritoneal metastases, 80% had gastric primary tumors, and 4% had microsatellite instability (MSI)–high or DNA mismatch repair protein–deficient tumors. PDL-1 expression by tumor area positivity (TAP) combining tumor and immune cell staining was ≥5% in 55% and <5% in 45%.

The primary endpoint of OS was improved with tislelizumab compared with placebo in patients with TAP ≥5% (median, 17.2% vs. 12.6 months; hazard ratio, 0.74; P=0.006); PFS was also significantly improved (HR, 0.67), and response rate was numerically improved. Among all treated patients, OS was also improved with tislelizumab over placebo (median, 15.0 vs. 12.9 months; HR, 0.80; P=0.001). The OS benefit for tislelizumab over placebo was diminished in patients with TAP <5% (HR, 0.92; 95% confidence limits, 0.75–1.13). The rate of serious treatment-related adverse events was higher with tislelizumab than placebo (23% vs. 15%). No new safety signals were observed.