Abstract 5292: Investigating the potential relationship between BRAF mutations and tumor mutation burden (TMB) in lung cancer (LC)
Authors: Zhang Jian , Fang Yu , Sun Lei , Yuan Hongling , Shang Mao , Zhang Xiaoyan , Zhu Honglin , Ma Tonghui 
Published: June 2022

BackgroundCurrently, BRAF inhibitors are primarily effective in LC patients with BRAF V600E mutation, while with limited benefit for patients with BRAF non-V600E mutation. Additionally, it is unclear whether immunotherapy is effective in LC patients with BRAF mutations, and the relationship between BRAF mutations and immune biomarkers, such as TMB, is also unclear. Here, we retrospectively investigated the relationship with BRAF mutation and TMB in Chinese LC patients.MethodsSamples were extracted from 3,136 our cohort samples of LC, which from OncoPanscan࣪ (Genetron Health) based sequencing of tissue. Because of the significantly different cohort characteristics, propensity score matching was used to resolve potential confounding by a nearest neighbor algorithm. The use of a multivariable logistic regression model to estimate the propensity score was based on age, sex, cancer type and detail panels. The samples after propensity score matching was used to investigate the relationship with TMB. ResultsIn our cohort, 171 samples had BRAF mutations and 2,965 samples had non-BRAF mutations. After propensity score analysis, 165 samples of BRAF mutations were screened with 165 paired samples of non-BRAF mutations.In the 165 samples of BRAF mutations, 83 samples of them had TMB information, while 83 samples of the 165 paired samples of non-BRAF mutations had TMB information. Patients with BRAF mutation had a higher median TMB than the patients with non-BRAF mutation (9.39 vs. 7.51 Muts/Mb, p=0.0545). Similarly, in these two groups, there was slightly higher ratio of samples with TMB ≥10muts/Mb (43.37% vs. 31.32%, P=0.0788). Among BRAF mutation group, when compared to BRAF V600E group (N=26), the median TMB was much higher in non-V600E group (N=57) (7.38 vs. 9.86 muts/Mb, P=0.0270). The proportion of TMB ≥10muts/Mb in BRAF non-V600E group was much higher than V600E group (49.12% vs. 30.77%, P=0.0094). Additionally, we analyzed the samples that had high TMB (TMB≥10 muts/Mb) and high PD-L1 (TPS≥50%). The BRAF mutation group had more proportion than non-BRAF mutation (14.46% vs.6.02%, p=0.0593), and the BRAF non-V600E group was higher than BRAF V600E group (15.79% vs. 11.54%, P=0.4150).ConclusionsCompared with non-BRAF mutation, BRAF mutation was associated with higher TMB, and it was also higher in BRAF non-V600E than BRAF V600E. These results suggested that patients with driver mutation of BRAF V600E had lower TMB and they always had good response to BRAF inhibitors. While LC patients with BRAF non-V600E always with higher TMB, thus, they may be more suitable for immunotherapy. However, more clinical research are needed to evaluate the effectiveness of immunotherapy.

Citation Format: Jian Zhang, Yu Fang, Lei Sun, Hongling Yuan, Mao Shang, Xiaoyan Zhang, Honglin Zhu, Tonghui Ma. Investigating the potential relationship between BRAF mutations and tumor mutation burden (TMB) in lung cancer (LC) [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 5292.