Background
Phase 3 RCT (PEARL); N=334 metastatic NSCLC, PD-L1 TPS ≥25%, EGFR/ALK wild-type, conducted mainly in Asia, comparing durvalumab monotherapy vs platinum-doublet chemotherapy first-line.
Interventions and follow up
Arm A: Durvalumab 1500 mg IV q4w
Arm B: Platinum-doublet chemotherapy, investigator's choice (e.g., gemcitabine-carboplatin) q3w
Primary endpoint: overall survival
mFollow up: ~13mo
Arm B: Platinum-doublet chemotherapy, investigator's choice (e.g., gemcitabine-carboplatin) q3w
Primary endpoint: overall survival
mFollow up: ~13mo
Results
mOS: 14.6mo vs 12.8mo, durvalumab vs chemo, HR 0.86, 95%CI 0.66-1.14, P=.30; not superior
mPFS: 3.9mo vs 5.5mo, HR 1.13, P=.54
ORR: 23.8% vs 35.6%
mPFS: 3.9mo vs 5.5mo, HR 1.13, P=.54
ORR: 23.8% vs 35.6%
Adverse events
Overall: grade ≥3 AEs 20% (durvalumab) vs 48% (chemo)
Chemo arm: cytopenias and nausea common
Durvalumab: no new safety signals
Chemo arm: cytopenias and nausea common
Durvalumab: no new safety signals
Conclusions
Durvalumab monotherapy did not improve survival over chemotherapy in PD-L1 ≥25% NSCLC, failing to replicate pembrolizumab monotherapy benefit in comparable populations.
Key Limitations
Negative trial; predominantly Asian population may limit generalizability; lower-than-expected PD-1/L1 monotherapy effect; chemo arm outperformed on PFS/ORR.
Clinical Context
Did not establish durvalumab monotherapy as a 1L option; reinforces that PD-(L)1 agents are not interchangeable. Pembrolizumab monotherapy (KEYNOTE-024) remains the high-PD-L1 standard; durvalumab is used 1L with chemo (POSEIDON) instead.
References