P37.16 Alterations in HRR Related Genes as Potential Markers of Clinical Benefit from PARP Inhibitor and PD-1/PD-L1 Blockade in Advanced Lung Cancer

Abstract

Homologous recombination repair (HRR) related gene alteration are associated with PARP inhibitor and increased tumor mutation burden (TMB). However, in lung cancer the detection of HRR gene is unclear, and its correlation with TMB has not been reported. We systematically investigated alteration genes in 578 Chinese lung cancer patients all samples were detected by hybridization capture-based NGS 1021-gene panel, which includes 36 HRR-related genes (see the gene list in below). We also evaluate the TMB of each patients. TMB analysis interrogated single nucleotide variants, small insertion and deletion, with VAF (variant allele frequency) ≥3 % (tissue) and ≥0.5 % (blood), respectively. TMB-high pts were identified with ≥9 mut/MB (upper quartile of data from geneplus). In this study, HRR related gene is the mainly germline mutation, percentage being about 66% (4). The percentage of HRR related gene somatic alteration in lung cancer is about 29% (168). Interesting, there 32% HRR alteration cases were found co-occurrence EGFR mutation but no significantly difference with non-EGFR cases(p=0.13). And also the percentage of BRCA1/2 mutation co-occurrence with EGFR mutation is no significantly difference with non-EGFR (14% vs 17%, p=0.44). On the other hand, TMB-high percentage in the case with HRR gene alteration is higher than the case without HRR related gene (49% vs 13%, p˂0.0001). In non-EGFR patients, the percentage of TMB-H is about 25% (92/365), and 51% (59/114) HRR alterations case without EGFR were TMB-H. So 20% (114/578) lung cancer patients who without EGFR mutation but with HRR related gene alteration could have a chance to consider medication of PARP inhibitor, and also 10% patients with TMB-high (59/578), maybe with higher efficacy of PD-1/PD-L1 blockade .