Tumor mutation load assessed by FoundationOne (FM1) is associated with improved efficacy of atezolizumab (atezo) in patients with advanced NSCLC

Abstract

Background: In patients ( pts) with NSCLC, the efficacy of atezo (anti-PDL1) correlates with PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC). We further examined the association between tumor mutation load (ML) and efficacy of atezo in pts with NSCLC. Methods: Pretreatment tumor specimens from 454 2L+ NSCLC pts treated on three Ph 2 trials of atezo monotherapy (POPLAR, a trial comparing atezo vs docetaxel (doc); BIRCH and FIR, single-arm studies in PD-L1-selected pts) were available for targeted genetic sequencing using the FM1 panel of 315 cancer-related genes. ML was quantified for each sample and efficacy was assessed in groups defined by 75th (high), 50th (median) and 25th (low) percentile of the study-specific ML. TIL infiltration was assessed by H&E staining. Teff gene expression was assessed with iChip. Atezo efficacy was examined at the following data cutoffs: POPLAR, May 8, 2015; BIRCH, May 28, 2015; FIR, Jan 7, 2015. Results: Across all samples, the median ML was 9.9/MB (range 0-444.1, 25th-75th percentile 6.3-16.6). OS, PFS and ORR were improved in pts with increased ML treated with atezo in both unselected pts (POPLAR) and PD-L1-selected pts (BIRCH, FIR; see Table). ML appeared to predict atezo efficacy independently of PD-L1 status. ML was not associated with efficacy in pts treated with doc in POPLAR. Associations of ML with PD-L1 expression on TC and IC, TIL infiltration and Teff gene expression will be presented. Conclusions:We demonstrated for the first time that increased tumor ML assessed by the FM1 targeted sequencing panel is associated with improved outcomes with atezo in 2L+ NSCLC. The association between ML and atezo efficacy was seen in both unselected and PD-L1-selected NSCLC pts. ML did not appear to be prognostic in pts treated with doc. Therefore, in addition to PD-L1, ML by FM1 may be an independent predictor of improved responsiveness to atezo in 2L+ NSCLC. (Table Presented).