Abstract 5774: Investigating the characteristics of BRAF Mutations and its potential relationship with therapy in a large Chinese Lung Cancer cohort
Authors: Zhang Jianqing , Feng Jiagang , Liu Ling , Jia Man , Liu Tong , Zhang Jiaqiang , Liao Zehua , Zhao Jianmei , Fang Yu , Chen Jing , Zhang Xiaoyan , Ma Tonghui 
Published: June 2022

Abstract
Background: In lung cancer, the proportion of BRAF mutations is low. Rare specific studies have evaluated the BRAF mutation characteristics in lung cancer. Currently, there are some studies suggesting that patients with BRAF mutations may be benefit from immunotherapy, while patients with BRAF V600E may benefit from targeted therapy. Here, the characteristics of BRAF mutation, including BRAF V600E, in a lung cancer cohort of Chinese were analyzed. The characteristics of BRAF mutation with PD-L1 expression were also analyzed. Method: BRAF mutant samples were extracted from 12,051 our cohort samples of lung cancer that from Onco Panscan࣪ (Genetron Health) based sequencing of tissue. The characteristics of them were then investigated. Co-mutations of PD-L1 expressed BRAF samples were also analyzed.
Results: 684 samples (5.68%) in our cohort had BRAF mutations. Only 134 (19.59%) of them were V600E mutation, maybe good response to BRAF inhibitors. 550 (80.41%) of samples were BRAF non-V600E mutation, maybe benefit from immunotherapy. BRAF mutations were more happened in male (58.3%), while female patients were increased in V600E mutation group when compared with non-V600E group (49.25% vs. 39.82%, P=0.0509). BRAF mutations were more likely to occur in LUAD than in LUSC (6.37% vs. 3.89%, P=0.0022), especially BRAF V600E mutation. The mean age of BRAF mutant patients was 61.56 ± 10.32 years. BRAF V600E patients was significantly older than BRAF non-V600E patients on average (63.01 ± 9.76 years vs. 61.20 ±10.43, P=0.0129). BRAF mutations were distributed across all exons but concentrated on exon 15 (269/684, 39.33%). Moreover, BRAF V600E mutation accounted for 49.81% (134/269) of exon 15. In our data, there were 108 samples with BRAF mutation and PD-L1 positive (TPS≥1%). Among them, 95 samples (87.96%), including samples with BRAF V600E or non-V600E mutation, had no co-mutations or without other medication targets, may be benefit from BRAF inhibitors, or may be good response to immunotherapy, especially the 20 samples with TMB-high. Interestingly, 13 samples had EGFR sensitive co-mutation or EML4-ALK fusion. These 13 patients may be benefit from TKI firstly, then immunotherapy can be considered.
Conclusions: Most of BRAF mutations in Chinese lung cancer samples were non-V600E mutations (80.26%). BRAF mutations were more occurred in male and LUAD patients whose age around 61.56 ± 10.32 years. BRAF V600E patients were much older. Among PD-L1 positive and BRAF mutant samples, most BRAF mutations (87.96%), including V600E, were mutually exclusive with driver mutations of other genes. These patients will most likely benefit from BRAF inhibitors or immunotherapy. For the samples with co-mutation of BRAF and EGFR or ALK, may be treated EGFR or ALK TKI firstly.
Citation Format: Jianqing Zhang, Jiagang Feng, Ling Liu, Man Jia, Tong Liu, Jiaqiang Zhang, Zehua Liao, Jianmei Zhao, Yu Fang, Jing Chen, Xiaoyan Zhang, Tonghui Ma. Investigating the characteristics of BRAF Mutations and its potential relationship with therapy in a large Chinese Lung Cancer cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5774.