4187 - Efficacy and safety evaluation based on time from completion of radiotherapy to randomization with durvalumab or placebo in pts from PACIFIC

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 with WHO PS 0/1 who did not progress after ≥2 cycles of platinum-based 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.

Clinical trial identification

PACIFIC [NCT02125461] released May 7, 2014.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Editorial Acknowledgement

Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Andrew Gannon, MS, of Cirrus Communications, an Ashfield company (Lyndhurst, NJ, USA), and was funded by AstraZeneca.

Disclosure

C. Faivre-Finn: Research funding: AstraZeneca, MSD. D.R. Spigel: Advisor/consultant: AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb Company, Genentech, Inc. S. Senan: Personal fees: AstraZeneca, Eli Lilly, MSD, Celgene; Research grant support: Varian Medical Systems, ViewRay, Inc. D. Raben: Consultant/advisory board member: AstraZeneca, EMD Serono, Genentech, Merck, Oncology Analytics. B. Perez: Advisory board: AstraZeneca, Bristol-Meyers Squibb outside the submitted work. A. Villegas: Speaker's bureau: AstraZeneca. R. Hui: Advisory board: AstraZeneca, MSD, Roche, Novartis, and BMS; Honoraria: AstraZeneca, MSD, Roche, Novartis. L. Paz-Ares: Scientific advice: BMS, Lilly, MSD, AstraZeneca, Roche, Pfizer, Novartis, Incyte, Merk, Boehringer. L. Poole: Contracted to work and holds a small number of shares: AstraZeneca. C. Wadsworth: Employed and holds a small number of shares: AstraZeneca. P.A. Dennis: Personal fees, full-time employment, and stock ownership: AstraZeneca. All other authors have declared no conflicts of interest.