A superior survival benefit with atezolizumab (atezo; anti–PD-L1) vs docetaxel (doc; HR 0.73; 95% CI: 0.62, 0.87) has been demonstrated in OAK, the first randomized Ph III study of atezo in NSCLC patients (pts) who had failed prior platinum therapy. In the primary efficacy population (n = 850), atezo benefit was seen regardless of PD-L1 expression levels on tumor cells (TC) or tumor-infiltrating immune cells (IC). Here, we present the analyses of irAEs in the safety population (N = 1225) of OAK.
Pts were randomized 1:1 to atezo (1200 mg) or doc (75 mg/m2) IV q3w. Co-primary endpoints were OS in ITT and in PD-L1 expression subgroups. Secondary endpoints included ORR and safety. 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. Safety analyses conducted were incidence, nature and severity of irAEs, corticosteroid use and irAEs leading to atezo interruption/discontinuation. Data cutoff: July 7, 2016.
In the atezo arm, 6.2% of pts had grade 3-4 irAEs and 25.0% of pts had grade 1-2 irAEs. No grade 5 irAEs were reported. Low rates of any-grade hypothyroidism (3.9%), pneumonitis (1.5%), hepatitis, (1.1%), and colitis (0.3%) were observed. Grade 3-4 irAEs included pneumonitis (0.7%) and hepatitis (0.7%); no pts developed Grade 3-4 colitis. 36 (5.9%) atezo arm pts experienced irAEs requiring corticosteroid treatment. Majority of irAEs in the atezo arm were manageable; 13 pts (2.1%) discontinued atezo. Meningoencephalitis (0.7%) and AST/ALT elevation (0.3%/0.2%) were the most frequently reported irAEs leading to atezo discontinuation. 26 pts (4.3%) had dose interruptions due to irAEs. AST/ALT elevation (0.8%/0.8%) and diarrhea (0.8%) were the most frequently reported irAEs leading to dose interruption.
The irAEs occurring in atezo-treated pts were mostly low grade and manageable, with few pts requiring dose interruption/discontinuation of atezo and corticosteroid treatment. Efficacy data based on irAE subgroups of OAK are presented separately.
Clinical trial identification
Legal entity responsible for the study
F. Hoffmann - La Roche Ltd.
F. Hoffmann - La Roche Ltd.
D. Cortinovis: Membership for AB for Roche, Novartis, MSD, BI. J. von Pawel: Adboard: AbbVie, Pfizer, Bristol Myers Squibb, Novartis money paid to the institution. R. Dziadziuszko: Honoraria or consulting fees from Roche, Pfizer, Boehringer‐Ingelheim, Clovis Oncology, Novartis, Astra‐Zeneca, Tesaro. 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. No other conflicts to report. F.S. Braiteh: COI: speaking and consulting fees received from Genentech. P. He: Employee of Roche/Genentech, and have stocks for Roche, Amgen. Husband has stocks for Allergan and Gilead. M. Ballinger: Employee of Genentech, Roche stock. M. Gandhi: Employee of Genentech. H. Patel: Genentech Employee. D.R. Gandara: Consultant: Genentech Clinical trial grant: Genentech. All other authors have declared no conflicts of interest.