Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC

Abstract

Background: Atezolizumab (atezo) inhibits the binding of PD-L1 to its receptors PD-1 and B7.1, thereby restoring tumor-specific T-cell immunity, while leaving the PD-L2/ PD-1 interaction intact. Atezo demonstrated survival benefit vs docetaxel (doc) in the Ph2 trial POPLAR. Here we present the primary analysis from the Ph3 OAK study evaluating atezo vs doc in previously treated NSCLC. Methods: Previously treated NSCLC patients ( pts) were stratified by PD-L1 status, prior chemotherapy regimens (1 vs 2) and histology, and randomized 1:1 to atezo (1200 mg IV q3w) or doc (75 mg/m2 IV q3w). The co-primary endpoints were OS in the ITT and PD-L1-expression subgroup TC1/2/3 or IC1/2/3 (PD-L1 expression on ≥ 1% TC or IC). Secondary endpoints included PFS, ORR, DoR and safety. Results: The primary efficacy analysis was conducted in the first 850 of 1225 total enrolled pts. Pts had a median age of 64 y, 61% were male, 25% had 2 prior lines of therapies, 26% had squamous histology, 67% were previous smokers and 37% were PS 0. Superior OS was seen with atezo vs doc in ITT (HR 0.73; P = .0003) and TC1/2/3 or IC1/2/3 pts (HR 0.74; P = .0102). Survival was improved regardless of PD-L1 expression levels, including in pts with no PD-L1 expression (TC0 and IC0). There was pronounced benefit in pts with high PD-L1 expression (TC3 or IC3). OS benefit was similar in pts with squamous or nonsquamous histology. In ITT pts, PFS HR was 0.95 (2.8 vs 4.0 mo), ORR 13.6% vs 13.4%, and DoR 16.3 vs 6.2 mo for atezo vs doc. Gr 3-4 treatment-related AEs occurred in 15% of atezo pts and 43% of doc pts. There were no deaths related to atezo and 1 related to doc. No new safety signal was observed. Conclusions: This first Ph3 trial of a PD-L1-directed drug in NSCLC demonstrates that atezo treatment results in a statistically significant and clinically relevant improvement in OS vs doc in 2L/3L NSCLC, regardless of PD-L1 expression and histology. Atezo was well tolerated with a favorable safety profile vs doc. (Table Presented).