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

IF 80.4 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2026-08-21 DOI:10.1016/j.annonc.2026.07.413

R H Xu, B C Cho, M Chen, K Muro, L Wyrwicz, B Li, S Gao, C Hsu, A Turpin, F Lordick, E Cha, Q Wu, S Kim, J Cai, L Zhang, J Fan, L Wang, K Sully, L Wang, K Goodman, M A Shah, I Chau

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引用次数: 0

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 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.

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Atezolizumab联合或不联合tiragolumab治疗晚期同步放化疗后不可切除的食管鳞状细胞癌（SKYSCRAPER-07）：一项随机III期研究。

背景：需要新的治疗方法来提高不可切除的食管鳞状细胞癌（ESCC）在明确放化疗（dCRT）后的生存率。在这种情况下，我们研究了atezolizumab±tiragolumab与安慰剂的疗效和安全性。患者和方法：SKYSCRAPER-07 （ClinicalTrials.gov: NCT04543617）是一项全球性、随机、安慰剂对照的III期试验，在28个国家的166个中心进行。接受dCRT治疗的II-IVA期局部晚期和选定的IVB期ESCC成年患者随机（1:1:1）接受阿特唑单抗1200mg +替拉单抗600mg，阿特唑单抗1200mg +安慰剂，或安慰剂+安慰剂（以下简称安慰剂），每3周静脉注射17个周期。分层测试的主要终点是研究者评估的无进展生存期（vv - pfs），然后是atezolizumab + tiragolumab与安慰剂的总生存期（OS），其次是atezolizumab +安慰剂与安慰剂的总生存期。结果：在2020年9月28日至2023年8月31日期间，760名患者被分配到atezolizumab + tiragolumab (n=257)， atezolizumab +安慰剂（n=250）或安慰剂（n=253）。总体而言，564例（74.2%）为男性，477例（62.8%）为亚洲人。在中位生存期随访25.0个月时，阿特唑单抗联合替拉单抗与安慰剂相比，没有统计学意义上改善INV-PFS（风险比[HR] 0.82, 95% CI 0.65-1.03; p=0.0947）或OS（风险比[HR] 0.91, 95% CI 0.70-1.18；描述性p=0.4772）。然而，与安慰剂相比，atezolizumab联合安慰剂组OS显著改善（HR 0.69, 95% CI 0.52-0.91；描述性p=0.0085）， INV-PFS组OS也显著改善（HR 0.74, 95% CI 0.58-0.93）。在atezolizumab + tiragolumab组、atezolizumab +安慰剂组和安慰剂组中，治疗相关的不良事件发生率分别为74.8%、65.2%和55.4%，治疗相关的死亡发生率分别为1.2%、0.8%和1.6%。结论：SKYSCRAPER-07研究没有达到主要终点。对于不可切除ESCC患者，阿特唑单抗加安慰剂与安慰剂在dCRT后的OS和PFS有临床意义的改善。临床试验号：NCT04543617。

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来源期刊

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.