139P - The characteristics in Chinese NSCLC patients with different BRAF mutation classes

Background

Compared with BRAF Class II and Class III mutations in non-small cell lung cancer (NSCLC), BRAF Class I mutations can be effectively targeted by inhibitors. However, the characteristics of Chinese NSCLC with different BRAF mutation types are still unclear. Thus, the more comprehensive exploration of BRAF mutation profile in Chinese NSCLC was investigated to guide the development of personalized treatment strategies.

Methods

Data was collected on a total of 2,030 cases of NSCLC throughout China between October 2018 and October 2021. Next Generation Sequencing (NGS) is based on the sequencing of tissue samples on the YUANSU^TM panel (OrigiMed, Shanghai, China) with 706 cancer-related genes. Wilcoxon Rank Sum Test were applied to significance statistics.

Results

Among the samples, BRAF mutations were detected in 82 cases (4.0%, 82/2030), including 19 Class I (0.9%, 19/2030, V600E), 13 Class II (0.6%, 13/2030, K601E, L597R/Q, G464V, G469A/V), and 11 cases Class III (0.5%, 11/2030, G466A/E, N581I, D594G/N). In addition, 39 cases (1.9%, 39/2030) remained unclassified: 22 (1.0%, 22/2030) with potential significance. The BRAF mutations were more commonly observed in primary tumors (p=0.066) and the Class I mutations were more prevalent in female patients (63.2%, 12/19, p=0.005). In addition, the median TMB (7.21 mut/Mb) of Class I mutations tumor was significantly lower than that of Class II mutations (median TMB =12.69 mut/Mb), III mutations (median TMB =22.32 mut/Mb) and unclassified BRAF mutations (median TMB =10.33 mut/Mb)(p = 0.033), implying that the patients with Class I mutations may not be suitable for immunotherapy compared with patients with Class II and III mutations. Furthermore, TP53, LRP1B, STK11, SPTA1and MAGI2 were significantly over-mutated in Class II and III (p<0.06) and SETD2 is over-mutated in Class I (p<0.001), might suggesting relatively poor prognosis in NSCLC patients.

Conclusions

The characteristics of Chinese NSCLC were further explored, including BRAF mutation types, the incidence of related co-mutations and TMB value, which is helpful to formulate targeted therapy strategies to adapt to different types of BRAF mutation functions according to their genomic and clinical characteristics.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

OrigiMed Inc.

Funding

OrigiMed Inc.

Disclosure

All authors have declared no conflicts of interest.