BACKGROUND: In the phase-3, placebo-controlled PACIFIC trial of patients with unresectable, stage III non-small-cell lung cancer (NSCLC) without disease progression after concurrent chemoradiotherapy (CRT), consolidative durvalumab was associated with significant improvements in the primary endpoints of overall survival (OS) (HR, 0.68; 95% CI, 0.53-0.87; P=0.00251; data-cutoff, 22-March-2018) and progression-free survival (PFS; blinded-independent-central-review; RECIST-v1.1) (HR, 0.52; 95% CI, 0.42-65; P<0.0001; 13-February-2017) with manageable safety. We report updated analyses of OS and PFS, approximately 4 years after the last patient was randomized.
METHODS: Patients with WHO PS 0/1 (any tumor PD-L1 status) were randomized (2:1) to intravenous durvalumab (10 mg/kg), or placebo, every-2-weeks (≤12 months), stratified by age, sex, and smoking history. OS/PFS were analyzed using a stratified log-rank test in the intent-to-treat population. Medians and 4-year OS/PFS rates were estimated by Kaplan-Meier method.
RESULTS: Overall, 709/713 randomized patients received durvalumab (n/N=473/476) or placebo (n/N=236/237). As of 20-March-2020 (median follow-up, 34.2 months; range, 0.2-64.9), updated OS (HR, 0.71; 95% CI, 0.57-0.88) and PFS (HR, 0.55; 95% CI, 0.44-0.67) remained consistent with the primary analyses. Median OS for durvalumab was reached (47.5 months; placebo, 29.1 months). Estimated 4-year OS rates were 49.6% versus 36.3% for durvalumab versus placebo, and 4-year PFS rates were 35.3% versus 19.5% respectively.
CONCLUSIONS: These updated, exploratory analyses demonstrate durable PFS and sustained OS benefit with durvalumab following CRT. An estimated 49.6% of patients randomized to durvalumab remain alive at 4 years (placebo, 36.3%), and 35.3% remain alive and progression free (placebo, 19.5%).