Background
Phase III open-label RCT, N=572, untreated stage IV nonsquamous or squamous NSCLC, wt-EGFR/wt-ALK, PD-L1 ≥1% (SP142 assay). Excluded active or untreated CNS mets.
Interventions and follow up
Arm A: Atezolizumab 1200 mg q3wk until progression
Arm B: Platinum-based chemotherapy* x4-6 cycles
Primary endpoint: OS (hierarchical by PD-L1 subgroup)
mFollow up: ~13-15 mo
Arm B: Platinum-based chemotherapy* x4-6 cycles
Primary endpoint: OS (hierarchical by PD-L1 subgroup)
mFollow up: ~13-15 mo
Results
PD-L1 strata: any (TC/IC ≥1%); high/intermediate (≥5%); high (TC ≥50% or IC ≥10%)
High PD-L1 mOS: 20.2 vs 13.1 mo (A vs B); HR 0.59, 95%CI 0.40-0.89; P=.01
High/intermediate PD-L1 mOS: 18.2 vs 14.9 mo; HR 0.72, 95%CI 0.52-0.99; P=.04 (did not cross prespecified alpha)
High PD-L1 mPFS: 8.1 vs 5.0 mo; HR 0.63, 95%CI 0.45-0.88
High/intermediate PD-L1 mPFS: 7.2 vs 5.5 mo; HR 0.67, 95%CI 0.52-0.88
High PD-L1 ORR: 38.3% vs 28.6%
High/intermediate PD-L1 ORR: 30.7% vs 32.1%
High PD-L1 mOS: 20.2 vs 13.1 mo (A vs B); HR 0.59, 95%CI 0.40-0.89; P=.01
High/intermediate PD-L1 mOS: 18.2 vs 14.9 mo; HR 0.72, 95%CI 0.52-0.99; P=.04 (did not cross prespecified alpha)
High PD-L1 mPFS: 8.1 vs 5.0 mo; HR 0.63, 95%CI 0.45-0.88
High/intermediate PD-L1 mPFS: 7.2 vs 5.5 mo; HR 0.67, 95%CI 0.52-0.88
High PD-L1 ORR: 38.3% vs 28.6%
High/intermediate PD-L1 ORR: 30.7% vs 32.1%
Adverse events
Overall (A vs B): grade 3-4 treatment-related 30.1% vs 52.5%
Immune-related: hypothyroidism, rash, hepatitis, pneumonitis more frequent with atezolizumab
Hematologic: cytopenias predominantly in chemotherapy arm
Immune-related: hypothyroidism, rash, hepatitis, pneumonitis more frequent with atezolizumab
Hematologic: cytopenias predominantly in chemotherapy arm
Conclusions
First-line atezolizumab monotherapy significantly improved OS in NSCLC with high PD-L1 expression, with less toxicity than chemotherapy.
Key Limitations
OS benefit confirmed only in the high-PD-L1 subgroup; intermediate/any subgroups not significant due to hierarchical testing. Uses SP142 assay (not interchangeable with 22C3). Open-label. CNS mets excluded.
Clinical Context
FDA approved first-line atezolizumab monotherapy for metastatic NSCLC with high PD-L1, no EGFR/ALK (May 2020). An alternative single-agent IO option to pembrolizumab for high expressers per ESMO. Chemotherapy*: nonsquamous = cisplatin/carbo + pemetrexed; squamous = cisplatin/carbo + gemcitabine.