Induction and consolidation atezolizumab with stereotactic body radiation therapy versus radiation alone in high-risk, early-stage non-small-cell lung cancer (SWOG/NRG S1914): a multicentre, open-label, superiority, phase 3, randomised controlled trial.

We aimed to test the addition of neoadjuvant, concurrent, and adjuvant atezolizumab with SBRT for early-stage NSCLC.

我们旨在测试将新辅助、同步和辅助atezolizumab与SBRT联合用于早期NSCLC的效果。

Methods

In this multicentre, open-label, phase 3, randomised controlled trial, eligible patients from 146 institutions across the USA who had T1-T3N0M0 NSCLC ≤7 cm, and were medically inoperable or declined surgery, and had at least one risk factor suggestive of increased risk of recurrence, were included in the study.

在这项多中心、开放标签、第三阶段、随机对照试验中，符合条件的患者来自美国146个机构，他们患有T1-T3N0M0 NSCLC ≤7 cm，医学上无法手术或拒绝手术，并且至少有一个风险因素表明复发风险增加，这些患者被纳入研究。

Patients underwent open-label equal and stratified randomisation to SBRT over three to eight fractions with or without up to eight cycles of neoadjuvant, concurrent, and adjuvant atezolizumab 1200 mg intravenously every 21 days for up to eight cycles, with SBRT initiated with cycle three.

患者进行了开放标签的平等和分层随机分配，接受SBRT治疗，分三到八次进行，有或没有最多八个周期的新辅助、同步和辅助atezolizumab 1200 mg静脉注射，每21天一次，最多八个周期，SBRT从第三个周期开始。

The primary objective was to compare overall survivalbetween the two groups.

主要目标是比较两组的总生存率。

The group sequential design included four interim analyses.

群体序贯设计包括四次中期分析。

Target accrual was 480 patients (432 eligible).

目标招募人数为480名患者（432名符合条件）。

The trial is registered with ClinicalTrials.gov (NCT04214262) and is closed to new participants.

该试验已在ClinicalTrials.gov注册（NCT04214262），并已停止接受新参与者。

Results

Between March 25, 2020, and Sept 9, 2024, 417 patients were enrolled and randomly assigned to atezolizumab plus SBRT (n=210) or SBRT alone (n=207). 402 were eligible and made up the modified intention-to-treatpopulation (201 per group).

在2020年3月25日至2024年9月9日期间，共有417名患者被纳入研究并随机分配到阿替利珠单抗联合立体定向放射治疗(SBRT)组(n=210)或仅接受SBRT组(n=207)。402名患者符合入选标准，构成了修正意向治疗人群（每组各201人）。

The median age was 72·8 years (IQR 67·4-78·4), 218 (54%) of 402 participants were female, and 184 (46%) were male.

中位年龄为72.8岁（四分位数间距67.4-78.4），402名参与者中有218名（54%）为女性，184名（46%）为男性。

Accrual closed at the first interim analysis of all randomly assigned participants for futility with 76 progression-free survival(PFS) events and 41 deaths among 400 eligible participants (200 per group).

在对所有随机分配的参与者进行的第一次中期分析中，由于无效性，招募工作已经关闭，共有76例无进展生存（PFS）事件和41例死亡，涉及400名符合条件的参与者（每组各200人）。

An updated analysis was performed with 140 PFS events, 92 deaths, and a median of 24·8 months (range 0·1-64·9; IQR 18·6-36·0) of follow-up among living patients.

在对140例PFS事件、92例死亡和中位随访时间为24.8个月（范围0.1-64.9；四分位数间距18.6-36.0）的存活患者进行的更新分析中。

The overall survivalhazard ratiowas 1·04 (95% CI 0·69-1·58; one-sided p=0·58).

总体生存风险比为1.04（95% CI 0.69-1.58；单侧p=0.58）。

Estimated 2-year overall survivalwas 82% in both groups (95% CI 75-87).

估计的2年总体生存率为两组均为82%（95% CI 75-87）。

Grade 3 or higher adverse eventrates were 12% with atezolizumab plus SBRT and 3% with SBRT.

阿替利珠单抗联合SBRT组的3级或更高级别的不良事件发生率为12%，而仅接受SBRT组为3%。

Two grade 5 respiratory events occurred in the atezolizumab plus SBRT group.

在阿替利珠单抗联合SBRT组中发生了两例5级呼吸系统事件。

interpretation

In the first fully reported phase 3 cooperative group trial to assess immunotherapy in inoperable early-stage NSCLC, we observed no improvement in overall survivalwith atezolizumab plus SBRT, and more grade 3 or higher adverse events were reported with atezolizumab combined with SBRT.

在首个全面报告的第3阶段合作组试验中，我们评估了不可手术的早期非小细胞肺癌（NSCLC）的免疫治疗，观察到阿替利珠单抗联合立体定向放疗（SBRT）并未改善总生存率，并且报告了更多的3级或更高级别的不良事件。

funding

US National Institutes of Health, US National Cancer Institute, and Genentech.

美国国家卫生研究院、美国国家癌症研究所和基因泰克。