Background
Phase 3, multicenter (146 US institutions), open-label, superiority randomized trial (SWOG/NRG S1914; NCT04214262). N=402 (modified ITT) with T1-T3N0M0 NSCLC ≤7 cm, medically inoperable or declined surgery, and ≥1 high-risk feature for recurrence. Stereotactic body radiation therapy (SBRT) ± atezolizumab. Primary endpoint overall survival.
Results
Interventions and follow up: Arm A: SBRT + neoadjuvant/concurrent/adjuvant atezolizumab 1200 mg IV q21d, up to 8 cycles (SBRT started with cycle 3) (n=201)
Arm B: SBRT alone (n=201)
Primary endpoint: overall survival (OS)
mFollow up: 24.8 months
Results: OS: HR 1.04 (95% CI 0.69-1.58, one-sided P=.58); closed early for futility at first interim
2-yr OS: 82% in both arms
PFS: no benefit
Arm B: SBRT alone (n=201)
Primary endpoint: overall survival (OS)
mFollow up: 24.8 months
Results: OS: HR 1.04 (95% CI 0.69-1.58, one-sided P=.58); closed early for futility at first interim
2-yr OS: 82% in both arms
PFS: no benefit
Adverse events
Grade ≥3 AE: 12% (atezolizumab + SBRT) vs 3% (SBRT alone)
Grade 5: 2 respiratory deaths with atezolizumab + SBRT
Grade 5: 2 respiratory deaths with atezolizumab + SBRT
Conclusions
Adding atezolizumab to SBRT did not improve overall survival or PFS in high-risk, early-stage inoperable NSCLC and increased toxicity. This is the first fully reported phase 3 cooperative-group trial of immunotherapy in this setting, and it is negative.
Key Limitations
Stopped early for futility, limiting events and power; open-label; heterogeneous SBRT fractionation; no PD-L1 selection; broad 'high-risk' eligibility definition; long-term data immature.
Clinical Context
SBRT alone remains the standard of care for medically inoperable early-stage NSCLC. Unlike stage III (PACIFIC) and resectable disease (perioperative immunotherapy), S1914 shows no role for concurrent/adjuvant atezolizumab added to SBRT in early-stage inoperable NSCLC; ongoing trials such as PACIFIC-4 continue to test the SBRT + immunotherapy concept.