First-line tislelizumab plus chemotherapy versus placebo plus chemotherapy in adults with advanced or metastatic esophageal squamous cell carcinoma: a Japanese subgroup analysis of RATIONALE-306 with ≥ 3 years of follow-up

BACKGROUND: In the global phase 3 RATIONALE-306 study (NCT03783442), first-line tislelizumab plus chemotherapy showed significant overall survival (OS) benefit versus chemotherapy alone for unresectable locally advanced/metastatic esophageal squamous cell carcinoma (ESCC). We report post hoc results for the Japanese subgroup. METHODS: Eligible Japanese patients were randomized (1:1) to tislelizumab 200 mg or placebo every 3 weeks plus chemotherapy (cisplatin plus fluoropyrimidine) and included in the Japanese analysis set. Endpoints included OS, progression-free survival (PFS), objective response rate (ORR), OS in patients with programmed death-ligand 1 (PD-L1) Tumor Area Positivity (TAP) score ≥ 10%, and safety. RESULTS: Overall, 66/649 (10.2%) patients were randomized in Japan (n = 33 per arm). After a minimum follow-up of 37.9 months (data cutoff November 24, 2023), tislelizumab plus chemotherapy showed improvements in median OS versus placebo plus chemotherapy (24.5 vs. 15.1 months; hazard ratio [HR]: 0.75; 95% CI 0.43-1.30). An improvement in OS was also seen in patients with PD-L1 TAP score ≥ 10% (HR: 0.79; 95% CI 0.26-2.36). There was improvement in median PFS (HR: 0.77; 95% CI 0.45-1.32) and a higher ORR (63.6% vs. 45.5%) in the tislelizumab plus chemotherapy versus placebo plus chemotherapy arm, respectively. Treatment-related adverse events (TRAEs) with tislelizumab plus chemotherapy versus placebo plus chemotherapy occurred in, respectively, 45.5% versus 36.4% (any-grade) and 27.3% versus 6.1% (grade ≥ 3) of patients. No TRAE-related deaths occurred. CONCLUSIONS: After 3 years, first-line tislelizumab plus chemotherapy demonstrated sustained efficacy and a tolerable safety profile in Japanese patients with unresectable locally advanced/metastatic ESCC, consistent with the global RATIONALE-306 population.