OAK, the first randomized Ph III study of atezolizumab (atezo; anti–PD-L1), demonstrated a superior survival benefit with atezo vs docetaxel (doc) in NSCLC patients (pts) who had failed prior platinum therapy (HR 0.73; 95% CI: 0.62, 0.87). This analysis evaluates the benefit of atezo in pts with and without irAEs from the primary efficacy population (n = 850) of OAK. Safety data are reported separately.
Pts were randomized 1:1 to atezo (1200 mg) or doc (75 mg/m2) IV q3w. irAEs were defined using MedDRA Preferred Terms that included both diagnosed immune conditions and signs and symptoms potentially representative of immune related events, regardless of investigator-assessed causality. For this analysis, efficacy was evaluated in pts with and without irAEs in the atezo and doc arms; efficacy endpoints were OS, PFS and ORR. To overcome the inherent survivor bias between irAE subgroups (pts surviving longer may be more likely to have irAEs), OS was evaluated using a time-dependent (TD) Cox model. Additional exploratory analyses included atezo efficacy in pts who did vs did not receive systemic steroids for irAEs. Data cutoff: July 7, 2016.
The incidence of irAEs in the atezo arm was 31% (25.0% grade 1-2, 6.2% grade 3-4, no grade 5). Baseline characteristics including PD-L1 expression on tumor cells or tumor-infiltrating immune cells were generally similar between irAE subgroups. OS per TD Cox model was in favor of atezo arm pts with irAEs vs those without irAEs (HR 0.79; 95% CI: 0.60, 1.05). Median time to onset of first irAE was 1.6 mo; post irAE mOS was 17.3 mo (95% CI: 11.7, 21.2). 24 atezo arm pts (6%) required corticosteroid treatment. Median OS in pts who did vs did not receive corticosteroids was 16.0 mo (95% CI: 10.3, 23.5; n = 24) vs 21.9 mo (95% CI: 16.6, NE; n = 106), respectively. Median PFS was 5.9 mo (95% CI: 2.6, 14.5) vs 5.4 mo (95% CI: 4.2, 8.8) and ORR was 29% (95% CI: 13, 51) vs 21% (95% CI: 13, 30) in pts who did vs did not receive corticosteroids.
In this analysis, irAEs did not negatively impact the survival benefit of atezo. Further investigation on the impact of corticosteroids on atezo efficacy in randomized trials is needed.
Clinical trial identification
Legal entity responsible for the study
F. Hoffmann - La Roche Ltd.
F. Hoffmann - La Roche Ltd.
J. von Pawel: Adboard: AbbVie, Pfizer, Bristol Myers Squibb, Novartis money paid to the institution. D. Cortinovis: Membership for AB for Roche, Novartis, MSD, BI. R. Dziadziuszko: Honoraria or consulting fees from Roche, Pfizer, Boehringer‐Ingelheim, Clovis Oncology, Novartis, Astra‐Zeneca, Tesaro. D.R. Gandara: Consultant: Genentech Clinical trial grant: Genentech. P. Conkling: Research funding is US Oncology Research. J. Goldschmidt: Honoraria: Amgen Consulting/Advisory Role: Amgen Speakers Bureau: Bristol Myers‐Squibb, Celgene. M. Kosty: Support limited to Institutional support for the reported trial and other clinical trials. No direct compensation to investigator. F.S. Braiteh: COI: speaking and consulting fees received from Genentech. S. Hu: Genentech employee and Roche stock. M. Ballinger: Employee of Genentech, Roche stock. H. Patel: Genentech Employee. M. Gandhi: Employee of Genentech. All other authors have declared no conflicts of interest.