Background
Phase III open-label RCT (IMpower010); N=1005; completely resected stage IB (≥4cm) to IIIA NSCLC after up to 4 cycles cisplatin-based adjuvant chemotherapy; randomized 1:1.
Interventions and follow up
Arm A: Atezolizumab 1200mg D1 Q21 x16 cycles (~1 yr)
Arm B: Best supportive care
Primary endpoint: Investigator-assessed DFS, hierarchically tested (PD-L1≥1% stage II-IIIA → all stage II-IIIA → ITT stage IB-IIIA)
mFollow up: 32.8 mo
Arm B: Best supportive care
Primary endpoint: Investigator-assessed DFS, hierarchically tested (PD-L1≥1% stage II-IIIA → all stage II-IIIA → ITT stage IB-IIIA)
mFollow up: 32.8 mo
Results
DFS, PD-L1≥1% stage II-IIIA: NR vs 35.3mo, HR 0.66, 95% CI 0.50-0.88, P=.0039
DFS, all stage II-IIIA: 42.3mo vs 35.3mo, HR 0.79, 95% CI 0.64-0.96, P=.020
DFS, ITT stage IB-IIIA: NR vs 37.2mo, HR 0.81, 95% CI 0.67-0.99, P=.040 (not formally significant per hierarchy)
DFS, all stage II-IIIA: 42.3mo vs 35.3mo, HR 0.79, 95% CI 0.64-0.96, P=.020
DFS, ITT stage IB-IIIA: NR vs 37.2mo, HR 0.81, 95% CI 0.67-0.99, P=.040 (not formally significant per hierarchy)
Adverse events
Overall: Grade 3-4 events 22% vs 12% (A vs B)
Immune-related: Grade 3-4 irAE 8% vs 1%; systemic corticosteroid use 12% vs 1%
Immune-related: Grade 3-4 irAE 8% vs 1%; systemic corticosteroid use 12% vs 1%
Conclusions
Adjuvant atezolizumab after chemotherapy improved DFS in resected stage II-IIIA NSCLC, with greatest benefit in PD-L1≥1% tumors, establishing a role for adjuvant immunotherapy.
Key Limitations
DFS surrogate endpoint with immature OS at primary analysis; open-label design; benefit concentrated in PD-L1≥1% subset; EGFR/ALK-positive patients now generally directed to targeted adjuvant therapy.
Clinical Context
FDA approved adjuvant atezolizumab for resected stage II-IIIA NSCLC with PD-L1≥1% (Oct 2021); EMA approval restricted to PD-L1≥50% without EGFR/ALK alterations. Sequenced after adjuvant platinum chemotherapy.