Atezolizumab (PD-L1) + SBRT Fails to Improve OS—and Adds Toxicity—in High-Risk Early-Stage NSCLC (SWOG/NRG S1914)

Atezolizumab is an anti–PD-L1 monoclonal antibody added as induction, concurrent, and consolidation therapy around curative-intent stereotactic body radiation therapy (SBRT) in medically inoperable (or surgery-declining) high-risk early-stage NSCLC. In the open-label Phase 3 SWOG/NRG S1914 trial (NCT04214262), 402 eligible patients with T1–T3N0M0 tumors ≤7 cm were randomized to SBRT alone vs atezolizumab 1200 mg IV q21d for up to 8 cycles with SBRT starting at cycle 3 (n=201/group); the study stopped early for futility, and with updated follow-up (median 24.8 months) OS was unchanged (HR 1.04, 95% CI 0.69–1.58; one-sided p=0.58) with 2-year OS 82% in both arms—within the expected SBRT-alone benchmark range in this medically inoperable population (~70% 2-year OS across meta-analyses/large series). Grade ≥3 AEs increased with atezolizumab (12% vs 3%), including 2 grade 5 respiratory events, signaling that routine IO intensification around SBRT is not justified without a better selection strategy.