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-labe

September 6, 2026| Source: Lancet (London, England)

Stereotactic body radiation therapy (SBRT) is the standard of care for early-stage, medically inoperable non-small-cell lung cancer (NSCLC). We aimed to test the addition of neoadjuvant, concurrent, and adjuvant atezolizumab with SBRT for early-stage NSCLC. 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. 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. The primary objective was to compare overall survival between the two groups. The group sequential design included four interim analyses. Target accrual was 480 patients (432 eligible). The trial is registered with ClinicalTrials.gov (NCT04214262) and is closed to new participants. 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-treat population (201 per group). The median age was 72·8 years (IQR 67·4-78·4), 218 (54%) of 402 participants were female, and 184 (46%) were male. 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). 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. The overall survival hazard ratio was 1·04 (95% CI 0·69-1·58; one-sided p=0·58). Estimated 2-year overall survival was 82% in both groups (95% CI 75-87). Grade 3 or higher adverse event rates were 12% with atezolizumab plus SBRT and 3% with SBRT. Two grade 5 respiratory events occurred in the atezolizumab plus SBRT group. In the first fully reported phase 3 cooperative group trial to assess immunotherapy in inoperable early-stage NSCLC, we observed no improvement in overall survival with atezolizumab plus SBRT, and more grade 3 or higher adverse events were reported with atezolizumab combined with SBRT. US National Institutes of Health, US National Cancer Institute, and Genentech.

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