Multicenter phase 3 trial of atezolizumab induction and consolidation added to SBRT in high-risk, early non-small cell lung cancer

Stereotactic body radiotherapy (SBRT) is the standard of care for early-stage medically inoperable non-small cell lung cancer NSCLC). The multicenter phase 3 SWOG/NRG S1914 trial evaluated addition of neoadjuvant, concurrent, and adjuvant atezolizumab to SBRT for early-stage NSCLC. A total of 417 patients from 146 centers across the USA were randomized to SBRT over three to eight fractions with (n=210) or without (n=207) up to eight cycles of atezolizumab 1200 mg intravenously every 21 days, with SBRT initiated with cycle three. The primary objective was to compare overall survival (OS) between the two groups. 402 participants 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). Accrual closed at the first interim analysis for futility with 76 progression-free survival (PFS) events and 41 deaths among 400 eligible participants (200 per group). Estimated 2-year OS 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. The authors conclude that addition of atezolizumab to SBRT for high-risk, early-stage inoperable NSCLC did not improve OS, while resulting in more grade 3 or higher adverse events.