Atezolizumab with or without tiragolumab in unresectable esophageal squamous-cell carcinoma following definitive concurrent chemoradiotherapy (SKYSCRAPER-07): a randomised, phase III study

BACKGROUND: New therapies are needed to improve survival in unresectable esophageal squamous cell carcinoma (ESCC) following definitive chemoradiotherapy (dCRT). We investigated the efficacy and safety of atezolizumab with or without tiragolumab versus placebo in this setting. PATIENTS AND METHODS: SKYSCRAPER-07 (ClinicalTrials.gov: NCT04543617) is a global, randomised, placebo-controlled, phase III trial carried out at 166 centres in 28 countries. Adult patients with stage II-IVA locally advanced and selected stage IVB ESCC who had received dCRT were randomly assigned (1 : 1 : 1) to receive atezolizumab 1200 mg plus tiragolumab 600 mg, atezolizumab 1200 mg plus placebo, or placebo plus placebo (hereafter placebo) intravenously every 3 weeks for 17 cycles. Hierarchically tested primary endpoints are investigator-assessed progression-free survival (INV-PFS) then overall survival (OS) with atezolizumab plus tiragolumab versus placebo, followed by OS with atezolizumab plus placebo versus placebo. RESULTS: Between 28 September 2020 and 31 August 2023, 760 patients were assigned to receive atezolizumab plus tiragolumab (n = 257), atezolizumab plus placebo (n = 250), or placebo (n = 253). Overall, 564 (74.2%) patients were male and 477 (62.8%) were Asian. At a median survival follow-up of 25.0 months, atezolizumab plus tiragolumab versus placebo did not statistically improve INV-PFS [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.65-1.03, P = 0.0947] or OS (HR 0.91, 95% CI 0.70-1.18, descriptive P = 0.4772). However, OS was significantly improved with atezolizumab plus placebo versus placebo (HR 0.69, 95% CI 0.52-0.91, descriptive P = 0.0085), as was INV-PFS (HR 0.74, 95% CI 0.58-0.93). Treatment-related adverse events occurred in 74.8%, 65.2%, and 55.4% of patients in the atezolizumab plus tiragolumab, atezolizumab plus placebo, and placebo groups, respectively, with treatment-related deaths occurring in 1.2%, 0.8%, and 1.6%, respectively. CONCLUSIONS: The SKYSCRAPER-07 study did not meet the primary endpoint. Clinically meaningful improvements in OS and PFS were demonstrated with atezolizumab plus placebo versus placebo following dCRT for patients with unresectable ESCC.