To explore the BRCA1/2 gene mutation frequency, the mutation types and the relationship between RCA1/2 gene mutation and efficacy of platinum-base chemotherapy in driver mutation-negative stage Ⅲ/Ⅳ non-small cell lung cancer.

All of 101patients with driver mutation-negative stage Ⅲ/Ⅳ NSCLC who were initially diagnosed and received platinum containing dual drug chemotherapy at the Respiratory and Critical Care Medical Center of the Second Affiliated Hospital Army Medical University, Fuling Hospital Affiliated to Chongqing University, Third Affiliated Hospital of Chongqing Medical University. BRCA1/2 gene mutations in tumor tissue/blood samples were detcted by Next Generation Sequencing (NGS). The treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). The primary endpoint was ORR, PFS, The secondary endpoints DCR, OS. The relationships between BRCA1/2 gene mutations and the efficacy of platinum containing chemotherapy were analyzed by medical statistics.

All of 101 driver mutation-negative stage Ⅲ/Ⅳ NSCLC patients were enrolled in this study. 19(18.8%) of 101 patients had BRCA1/2 gene mutations. The mutation types of BRCA1/2 include single nucleotide polymorphism, insertion and deletion; The mutation pattern include missense mutation, nonsense mutation, inframe insertion, frameshift deletion, and frameshift insertion. BRCA1/2 gene mutation group and BRCA1/2 gene wild-type group was no statistical difference in demographic baseline characteristics. After receiving 4-6 cycles of standard first-line platinum-base dual drug chemotherapy, the objective response rate (ORR 68.4% vs. 36.6%, P=0.019) and disease control rate (DCR 100% vs. 76.8%, P=0.020) of the BRCA1/2 gene mutation group was significantly higher than that of the BRCA1/2 gene wild type group. In contrast to the BRCA1/2 gene wild type group, the BRCA1/2 gene mutation group has longer median PFS(mPFS, 8.0 months vs. 4.6 months, P=0.009, HR 0.537, 95%CI: 0.351-0.821), while the median OS(mOS)just has lengthen tendency but no significantly different (19.4 months vs. 16.4 months, P=0.631, HR 0.866, 95%CI 0.491-1.528). In the subgroups of BRCA1 and BRCA2 gene mutations, there was no statistically significant difference in ORR (66.7% vs. 64.3%, P=0.567), PFS (13.7 months vs. 7.8 months, P=0.145) and OS (24.0 months vs. 14.4 months, P=0.142).

BRCA1/2 gene mutations frequency is about 18.8% in driver mutation-negative stage Ⅲ/Ⅳ NSCLC. The most common mutation types of BRCA1/2 gene is single nucleotide polymorphism and the most common mutation pattern is missense mutation. Driver mutation-negative stage Ⅲ/Ⅳ NSCLC patients with BRCA1/2 gene mutations may be more easy benefit from first-line platinum containing dual drug chemotherapy.