Tislelizumab Improves Survival in Patients with Esophageal Squamous Cell Cancer

FDA-approved treatments for metastatic esophageal squamous cell cancer include pembrolizumab or nivolumab plus chemotherapy in the first line, ipilimumab plus nivolumab without chemotherapy in the first line, and single-agent pembrolizumab or nivolumab in the second line. Investigators now report results of the international, industry-sponsored, phase 3 RATIONALE-306 trial evaluating the addition of the anti-PD-1 agent tislelizumab to chemotherapy in metastatic esophageal squamous cell cancer.

Patients were randomized to receive either tislelizumab (200 mg) or placebo on day 1 of 21-day cycles along with investigator's choice of chemotherapy — oxaliplatin or cisplatin combined with capecitabine, continuous-infusion 5-FU, or paclitaxel. Of the 649 patients, 75% were treated in Asia, 33% had prior surgery, and 12% had received definitive radiation therapy. The PD-L1 tumor area positivity (TAP) score was >10% in 34%, <10% in 49%, and unknown in 16%. A platinum/fluoropyrimidine was given to 45% of patients and platinum/paclitaxel to 55%.

The primary endpoint, median overall survival in all patients, was superior for tislelizumab compared with placebo (17.2 vs. 10.6 months; hazard ratio, 0.66; P<0.0001). Overall survival was improved with tislelizumab compared with placebo in patients with TAP scores <10% (15.8 vs. 10.4 months) and in those with TAP scores >10% (16.6 vs. 10.0 months). Median progression-free survival was also improved with tislelizumab compared with placebo (7.3 vs. 5.6 months; HR, 0.62; P<0.0001) and response rate was higher (63% vs. 42%; odds ratio, 2.38; P<0.0001). Serious treatment-emergent adverse events occurred more frequently with tislelizumab (29%) than placebo (19%).