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

In brief

Atezolizumab after chemoradiotherapy reduces death risk by one third in esophageal cancer

In the phase III SKYSCRAPER-07 trial, adding atezolizumab (without the experimental antibody tiragolumab) after definitive chemoradiotherapy improved overall survival by roughly 30% and progression-free survival by about 25% compared with placebo in unresectable esophageal squamous cell carcinoma. The combination with tiragolumab showed no benefit, and immune-related side effects were common but manageable.

Journal
Annals of oncology : official journal of the European Society for Medical Oncology (Q1)
Published
21 August 2026
Study design
Randomized controlled trial
Evidence level
Level 1, High (CEBM 1b)
Authors
R-H Xu, B C Cho, M Chen, K Muro, L Wyrwicz, B Li, et al.
PMID
42628839
DOI
10.1016/j.annonc.2026.07.413

Why clinicians should know about it

Abstract

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 ± tiragolumab versus placebo in this setting. PATIENTS AND METHODS: SKYSCRAPER-07 (ClinicalTrials.gov: NCT04543617) is a global, randomised, placebo-controlled, phase III trial performed at 166 centres in 28 countries. Adult patients with stage II-IVA locally advanced and selected stage IVB ESCC who had received dCRT were randomised (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 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% 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%. 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. CLINICAL TRIAL NUMBER: NCT04543617.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.