Tislelizumab Superior to Second-Line Chemotherapy in Esophageal Squamous Cancer

Immune checkpoint inhibitors have advanced in the treatment of metastatic squamous cancer of the esophagus, with regulatory approval for nivolumab and pembrolizumab in second-line treatment and recent approval for the addition of pembrolizumab to chemotherapy in first-line treatment. There is ongoing debate about the benefit of these agents in patients with low combined positive scores.

Investigators now report results of the RATIONALE-302 trial, a multinational, industry-sponsored, open-label, phase 3 trial comparing the anti–PD-1 antibody tislelizumab to chemotherapy in the second-line treatment of metastatic squamous cancer of the esophagus. Of 512 patients randomized to tislelizumab or investigator's choice of docetaxel, paclitaxel, or irinotecan, 80% were treated in Asia, 50% had PDL-1 tumor area positive (TAP) scores <10%, 65% had received prior radiotherapy, and 38% had prior surgery.

The primary endpoint of overall survival was significantly improved with tislelizumab compared with chemotherapy (median, 8.6 vs. 6.3 months; hazard ratio, 0.70; P=0.0001). Twelve-month survival was also higher in the tislelizumab arm (37.4% vs. 23.7%). Survival benefits were seen both in patients with TAP >10% (HR, 0.54) and in those with TAP <10% (HR, 0.82). Tislelizumab compared with chemotherapy improved both progression-free survival (HR, 0.83) and response rate (20.3% vs. 9.8%). There were no new safety signals.