Multinational phase 3 study of first-line tiragolumab plus atezolizumab and chemotherapy for unresectable or metastatic esophageal squamous cell carcinoma

The phase 3 SKYSCRAPER-08 trial, at 67 centers in China, South Korea, Thailand, Taiwan, and Hong Kong, evaluated addition of tiragolumab (anti-TIGIT) and atezolizumab (anti-PD-L1) to first-line chemotherapy for unresectable or metastatic esophageal squamous cell carcinoma (U/M ESCC). Adult patients with treatment-naïve U/M ESCC and an ECOG performance status 0 or 1 were randomized 1:1 to six cycles of tiragolumab plus atezolizumab and paclitaxel-cisplatin chemotherapy (n=229) or placebo plus chemotherapy (n=232). The primary outcomes were independent review facility-assessed progression-free survival and overall survival. Median survival follow-up was 12.6 months (IQR 6.8-18.0). Median PFS was 6.2 months in the tiragolumab-atezolizumab-chemotherapy group versus 5.4-months in the placebo-chemotherapy group (HR 0.56; p<0.0001), whereas median OS was 15.7 months versus 11.1 months (HR 0.70; p=0.0024), respectively. Serious adverse events occurred in 41% of patients in the tiragolumab-atezolizumab-chemotherapy group versus 39% of patients in the placebo-chemotherapy group, whereas treatment-related deaths occurred in six versus two patients, respectively. No new safety signals were identified. The authors conclude that addition of tiragolumab and atezolizumab to first-line chemotherapy for U/M ESCC was associated with improvement of PFS and OS.