PL04a.02: OAK, a Randomized Ph III Study of Atezolizumab vs Docetaxel in Patients with Advanced NSCLC: Results from Subgroup Analyses

Abstract

Atezolizumab inhibits PD-L1 binding to its receptors PD-1 and B7.1, thereby restoring tumor-specific T-cell immunity. Primary analysis of the Phase III OAK study in previously-treated NSCLC revealed superior survival for atezolizumab vs docetaxel in the ITT population (mOS, 13.8 vs 9.6 months; HR, 0.73) and in patients 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. OAK evaluated atezolizumab vs docetaxel in an unselected NSCLC population who had failed prior platinum-containing chemotherapy. Patients were stratified by PD-L1 expression, prior chemotherapy regimens and histology, and randomized 1:1 to atezolizumab (1200 mg) or docetaxel (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. For the first 850 of 1225 randomized patients (primary study population), OS was improved with atezolizumab vs docetaxel regardless of histology and this benefit was observed across PD-L1 subgroups within each histology (Table). PD-L1 gene expression showed a similar association with OS as PD-L1 IHC. In nonsquamous patients ORR was 14.4% vs 15.2%; in squamous patients ORR was 11.6% vs 8.2% (atezolizumab vs docetaxel). OS benefit vs docetaxel was seen across subgroups including patients 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. OAK demonstrated clinically relevant improvements with atezolizumab 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 in patients with baseline brain metastases.Tabled 1OSAtezolizumabDocetaxelHRa 95% CInMedian, monMedian, moNonsquamousTC3 or IC34922.5478.70.35(0.21-0.61)TC2/3 or IC2/38918.79911.30.61(0.42-0.88)TC1/2/3 or IC1/2/317117.616211.30.72(0.55-0.95)TC0 and IC014014.015011.20.75(0.57-1.00)All31315.631511.20.73(0.60-0.89)SquamousTC3 or IC32317.51811.60.57(0.27-1.20)TC2/3 or IC2/34010.4379.70.76(0.45-1.29)TC1/2/3 or IC1/2/3709.9608.70.71(0.48-1.06)TC0 and IC0407.6497.10.82(0.51-1.32)All1128.91107.70.73(0.54-0.98)aUnstratified HRs.TC=tumor cell, IC=tumor-infiltrating immune cell. Open table in a new tab