Results from OAK subgroup analyses: A randomized Phase III study of atezolizumab vs docetaxel in patients (pts) with advanced NSCLC

Abstract

Background: Atezolizumab (atezo) prevents binding of PD‐L1 to its receptors PD‐1 and B7.1, restoring tumor‐specific T‐cell immunity. Primary analysis of the Phase III OAK study in previously treated NSCLC showed superior survival with atezo vs docetaxel (doc) in the ITT population (mOS, 13.8 vs 9.6 months; HR, 0.73) and in pts expressing 1% PD‐L1 on TC or IC (TC1/2/3 or IC1/2/3; mOS, 15.7 vs 10.3; HR, 0.74). Here we present further subgroup analyses. (Table presented) Methods: OAK evaluated atezo vs doc in PD‐L1 unselected NSCLC pts who had failed prior platinum‐containing chemotherapy. Pts were stratified by PD‐L1 expression prior chemotherapy regimens and histology and randomized 1:1 to atezo (1200 mg) or doc (75 mg/m2) IV q3w. PD‐L1 expression by IHC and mRNA was centrally evaluated by VENTANA SP142 IHC assay and Fluidigm, respectively. Data cutoff, July 7, 2016. Results: In the first 850 of 1225 randomized pts (primary study population), OS was improved with atezo vs doc regardless of histology, and this benefit was seen across PDL1 subgroups within each histology (Table). Similar OS was seen regardless of PD‐L1 expression as assessed by mRNA and IHC. ORR was 14.4% vs 15.2% in non‐squamous (non‐sq) pts and 11.6% vs 8.2%(atezo vs doc) in squamous (sq) pts. Improved OS was seen with atezo vs doc across subgroups, including pts with treated baseline brain metastases (n=85; mOS, 20.1 vs 11.9 mo; HR, 0.54; 95% CI, 0.63, 0.89) and never smokers (n=156; mOS, 16.3 vs 12.6 mo; HR, 0.71; 95% CI, 0.47, 1.08). Further secondary endpoints and exploratory biomarker analyses for these subgroups and by age and EGFR/KRAS status will be presented. Conclusions: OAK demonstrated clinically relevant improvements with atezo in the ITT population, including in both histology subgroups, regardless of PD‐L1 expression (measured by IHC or tumor gene expression), and among other subgroups, including never smokers and pts with baseline brain metastases.