Background: Most patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) progress despite standard platinum-based, concurrent chemoradiation therapy (cCRT). We report interim results for clinical activity, patient-reported outcomes (PROs), and safety from a global, Phase 3 study (NCT02125461) of durvalumab as consolidation therapy in Stage III patients.
Methods: In this double-blind study, patients with WHO PS 0/1 (any PD-L1 status) who received ≥2 platinum-based cCRT cycles without progression were randomized (2:1) 1–42 days post-cCRT to durvalumab 10 mg/kg IV Q2W or placebo up to 12 months, stratified by age, sex, and smoking history. Co-primary endpoints were progression-free survival (PFS; blinded independent central review, RECIST v1.1) and overall survival (OS). Secondary endpoints included 12- and 18-month PFS rates, objective response rate (ORR), duration of response (DoR), time to death or distant metastasis (TTDM), PROs (EORTC QLQ-C30 and QLQ-LC13) and safety.
Results: Of 713 randomized patients, 709 received treatment (durvalumab, n=473; placebo, n=236). Baseline characteristics were well balanced. At cutoff, median follow-up was 14.5 months. Median PFS from randomization was significantly longer with durvalumab (16.8 months, 95% CI, 13.0–18.1) versus placebo (5.6 months, 95% CI, 4.6–7.8; stratified HR 0.52, 95% CI, 0.42–0.65; P<0.0001). 12- and 18-month PFS rates were 55.9% versus 35.3% and 44.2% versus 27.0%, respectively. ORR was higher (28.4% vs 16.0%; P<0.001) and median DoR longer (not reached vs 13.8 months) with durvalumab. Median TTDM was longer with durvalumab (23.2 vs 14.6 months; stratified HR 0.52, 95% CI, 0.39–0.69; P<0.0001). OS data were immature. Comparing durvalumab with placebo, grade 3/4 AEs occurred in 29.9% and 26.1%; most common was pneumonia (4.4% vs 3.8%). 15.4% and 9.8% discontinued due to AEs. PROs will be presented.
Conclusions: Durvalumab demonstrated a statistically significant, robust improvement in PFS, supported by secondary endpoints. No new safety signals were identified.