Efficacy and safety evaluation based on time from completion of radiotherapy to randomization with durvalumab or placebo in pts from PACIFIC

Abstract

Background: In the Ph 3 PACIFIC study of durvalumab (durva) versus placebo (pbo) in pts with stage III, locally advanced (LA), unresectable NSCLC after concurrent chemoradiotherapy (cCRT), PFS was significantly longer with durva (stratified HR 0.52; 95% CI 0.42-0.65; P<0.0001). This exploratory analysis characterizes outcomes based on time from completing RT to Tx. Methods: PACIFIC (NCT02125461) was a randomized, double-blind, all-comers study of LA NSCLC pts withWHOPS 0/1 who did not progress after ≥2 cycles of platinumbased cCRT. Pts were stratified by age, sex and smoking history and randomized (2:1) to durva 10 mg/kg IV Q2W or pbo up to 12 months. Co-primary endpoints were PFS (BICR, RECIST v1.1) and OS (not available). Secondary endpoints included ORR, time to death/distant metastases (TTDM) and safety. We investigated potential associations between time to randomized Tx (<14 or≥14 days) with efficacy and safety. Results: As of Feb 13, 2017, 713 pts were randomized, 26% within 14 days of RT. Baseline characteristics between the durva and pbo arm were well balanced in both the <14 and≥14 days groups. PFS benefit with durva compared to pbo was observed regardless of timing from RT to randomization (<14 days: median NR vs 4.8 months, HR=0.39, 95% CI: 0.26-0.58;≥14 days: median 14.0 vs 5.6 months, HR=0.63, 95% CI: 0.49-0.80). In addition, TTDM (<14 days: HR=0.33, 95% CI: 0.20-0.55;≥14 days: HR=0.70, 95% CI: 0.51-0.95) and ORR (<14 days: 34.2% vs 16.4%; ≥14 days: 26.5% vs 15.8%) favored durva, regardless of time to randomization. There were no reported differences in safety with durva based on time to randomization, with incidences of any-cause grade 3/4 AEs (34.2% vs 31.3%) and SAEs (30.0% vs 28.2%) comparable across subgroups. In contrast, earlier randomization in the pbo arm was associated with increased rates of grade 3/4 AEs (33.3% vs 25.9%) and SAEs (33.3% vs 19.0%). Early randomization had minimal impact on grade ≥3 pneumonitis/radiation pneumonitis with durva (4.2% vs 4.5%). Conclusions: Durva provided clinical benefit compared to pbo, regardless of time from RT to randomization. There was no meaningful difference in safety, including high grade AEs, in durva-treated patients randomized within 2 weeks from RT versus later.