Retrospective analysis of efficacy of immune checkpoint inhibitors in BRCA-mutant non-small cell lung cancer.

Abstract

e21067 Background: Efficacy of BRCA1/2 inhibitor in non-small cell lung cancer (NSCLC) is under investigation in serval clinical trials. Meanwhile immune checkpoint inhibitor (ICI) has become one of the standard therapies for advanced NSCLC, while its efficacy in BRCA mutant NSCLC is not clear. This study assessed the efficacy of anti-PD-(L)1/CTLA-4 in advanced BRCA-mutant NSCLC. Methods: Data of cohort OAK, POPLAR and Rizvi et al.,2018 was downloaded. Efficacy including objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were reviewed for BRCA1/2 mutant and wild-type group. The impact of mutant gene ( BRCA1, BRCA2), histological types (adenocarcinoma, squamous) and tumor mutation burden ranges (TMB, > 10 SNVs/Mb, < 10 SNVs/Mb) was analyzed if information was available. Results: A total of 809 ICI-treated advanced NSCLC patients, including 53 (6.6%) with BRCA1/2 mutation, were identified. In OAK/POPLAR cohort (atezolizumab monotherapy, 2nd line or more), TMB in BRCA1/2 mutant group was significant higher (19.2 vs. 10.24, P=0.008) than group of wild-type. The ORR of mutant group was 21.9% (Table), median PFS was 2.5 months, median OS was 9.5 months. The ORR and PFS were comparable between mutant and wild-type groups, while OS of the mutant group was significantly shorter than that in wild-type group (mOS, 9.5 months vs. 14.1 months, P= 0.02). Within mutant group, no significant difference of ORR, PFS and OS were found between mutant gene ( BRCA1 vs. BRCA2), histological type (adenocarcinoma vs. squamous) and TMB range (>10 vs. <10). In Rizvi’s cohort (anti-PD-(L)1 /CTLA-4 mono- or combination therapy, 1st line or more), TMB in mutant group was also significant higher (22.2 vs. 9.1, P=0.04) than wild-type group. ORR, PFS for mutant and wild-type groups were 25.0% vs. 20.1%, 3.2 months vs. 3.4 months, without significant difference. Within mutant group, superior PFS was found in adenocarcinoma subgroup (mPFS, 5.5 months vs. 1.2 months (squamous subgroup), P = 0.008) and BRCA2-mutant subgroup tend to have superior PFS (mPFS 5.5 months vs. 1.8 months, P=0.08) than BRCA1-mutant subgroup. Conclusions: This retrospective multicohort analysis showed a trend of worse survival in BRAC-mutant NSCLC patients after ICI treatment compared to those in wild-type group, in spite of higher TMB level. Analysis with more samples are needed to provide more precise treatment reference. [Table: see text]