Overall Survival with Durvalumab versus Placebo after Chemoradiotherapy in Stage III NSCLC: Updated Results from PACIFIC

Background In the Phase 3 PACIFIC study durvalumab significantly improved progression-free survival (PFS) versus placebo in Stage III, unresectable NSCLC patients without progression after chemoradiotherapy (CRT) (stratified HR, 0.52; 95% CI, 0.42 – 0.65; P < 0.001). Here we report the second primary endpoint overall survival (OS).

Methods Patients (WHO PS 0/1, any PD-L1 tumor status) who received ≥ 2 cycles of platinum-based CRT were randomized (2 : 1) 1 – 42 days post-CRT to durvalumab 10 mg/kg IV Q2W or placebo up to 12 months, stratified by age, sex, and smoking history. Primary endpoints were PFS (BICR, RECIST v1.1) and OS (interim analysis). Secondary endpoints were time to death/distant metastasis (TTDM), PFS2 (time to second progression), safety and time to 1st/2nd subsequent therapy or death (TFST/TSST).

Results 713 patients were randomized (709 with treatment: Durvalumab, n = 473; placebo, n = 236). As of 22-Mar-2018 median follow-up duration was 25.2 months (range, 0.2 – 43.1). After discontinuation 41.0% and 54.0% in the durvalumab and placebo groups received subsequent anticancer therapy; overall, 8.0% and 22.4% received additional immunotherapy. Durvalumab significantly improved OS versus placebo (stratified HR 0.68, 99.73% CI, 0.469 – 0.997; P = 0.00 251), with the median not reached (NR; 95% CI, 34.7 months–NR) and 28.7 months (95% CI, 22.9–NR). Durvalumab improved OS in all pre-specified subgroups. Updated PFS remained similar (stratified HR 0.51, 95% CI, 0.41 – 0.63), with medians of 17.2 and 5.6 months with durvalumab and placebo. Durvalumab improved the updated TTDM (stratified HR 0.53, 95% CI, 0.41 – 0.68) as well as PFS2 (stratified HR 0.58, 95% CI, 0.46 – 0.73), TFST (stratified HR 0.58, 95% CI, 0.47 – 0.72) and TSST (stratified HR 0.63, 95% CI, 0.50 – 0.79). Within the durvalumab and placebo groups, 30.5% and 26.1% had grade 3/4 any-causality AEs, 15.4% and 9.8% discontinued due to AEs. No new safety signals were identified.

Conclusions Durvalumab demonstrated statistically significant and clinically meaningful improvement in OS compared with placebo, supported by secondary endpoints such as PFS2. PACIFIC is the first study to show a survival advantage following CRT in this population, providing compelling evidence for the unprecedented benefit of durvalumab treatment as the standard of care.