Durvalumab Versus Chemotherapy as First-line Treatment for Metastatic NSCLC With Tumor PD-L1 Expression ≥25%: Results from the Randomized Phase 3 PEARL Study.

Introduction: PEARL (NCT03003962) is an open-label, phase 3 study comparing first-line durvalumab monotherapy with chemotherapy in patients with metastatic non-small cell lung cancer (mNSCLC [EGFR/ALK wild type]) with PD-L1 tumor cell (TC) membrane expression status ≥25%. We report the final analysis of PEARL.

Methods: Adults (N=669) with previously untreated Stage IV mNSCLC were randomized (1:1) to durvalumab 20mg/kg every 4 weeks or chemotherapy every 3 weeks for 4 to 6 cycles. Dual primary endpoints were overall survival (OS) in the PD-L1 TC ≥25% and the PD-L1 TC ≥25% low risk of early mortality (LREM) populations.

Results: Durvalumab was associated with a numerical reduction in the risk of death versus chemotherapy in the PD-L1 TC ≥25% population (OS hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.71, 0.99, p = 0.037; median OS 14.6 months [95% CI: 12.2, 16.9] versus 12.8 months [95% CI: 10.1, 14.7], respectively). In the PD-L1 TC ≥25% LREM population the OS HR for durvalumab versus chemotherapy was 0.96 (95% CI: 0.79, 1.15, p = 0.628); median OS 14.6 months (95% CI: 12.6, 17.2) versus 15.0 months (95% CI: 13.1, 16.8), respectively. In the safety population, the incidence of grade 3/4 treatment-related adverse events was 15.5% (durvalumab) and 45.9% (chemotherapy).

Conclusions: Durvalumab did not statistically significantly improve OS versus chemotherapy as first-line treatment in patients with mNSCLC and PD-L1 TC ≥25%. The numerical improvement in OS was consistent with previous studies of first-line immune checkpoint inhibitor monotherapy in patients with mNSCLC.