P90.01 Clinical Characteristics and Outcome of Patients with Non-Small Cell Lung Cancer Harboring BRAF Mutations

Abstract

Introduction: BRAF mutations occur 1%-4% in nonesmall-cell lung cancer, and the natural history of tumors harboring these mutations remains an area of ongoing study. The aim of this retrospective study was to describe the natural history, occurrence of co-mutations and clinical outcomes in patients with BRAF-mutated NSCLC. Methods: Patients with BRAF-mutated NSCLC seen at Affiliated cancer hospital of Zhengzhou university from January 1, 2017 through December 31, 2019 were reviewed. The Kaplan-Meier method was used to calculate median progression free survival (PFS) and median overall survival, and the COX regression model was established to analyze the association between the overall survival and various factors. Results: NGS (Next Generation Sequencing) data of either plasma or tissue samples obtained from 3217 Chinese stage I-IV NSCLC patients were retrospectively analyzed, 46 (1.4%) patients were found to have BRAF mutation, including 35(76%) V600E mutation and 11non-V600E mutation. Concomitant mutations had been also discovered, it's a more tendency for V600E mutation to had a concomitant mutation, Among 35 NSCLC with V600E mutation, 2 had a concomitant mutation in EGFR 19 exon deletion,1 in EGFR 21exon L858R mutation,1 inTP53 mutation and 1 in PIK3CA mutation; However, in the 11 non-V600E mutation, no concomitant mutation was found, but 2 with MET amplification. Clinical and pathological features were similar between patients with V600E vs non-V600E mutations.The average age was 62 years old ( 43-84). 25(54%) males and 27(58%) never smoker, 3(7%) light smoker and 16(35%) heavy smoker. The vast majority (93%,43/46) of pathological type was adenocarcinoma, other types including 1 squamous carcinoma and 2 with difficult histological classification. 42 were advanced stage at diagnosis, while 4 were early stage. The common metastasis sites was lung, pleural effusion, liver and adrenal gland. Retroperitoneal lymph node metastasis was also found frequently (17%,8/46). In the advanced and recurrent NSCLC with BRAF mutation, 25 patients had detailed treatment record and follow up information. Most (20/25) of them had chose chemotherapy ± bevacizumab as first line, while the rest accepted other treatment, including 1 chemotherapy combined with pembrolizumab, 3 Icotinib and 1 vandetanib. The Overall Response Rate (ORR) of first line was 44% (11/25) and median PFS was 8.67m(6.9m-10.5m). After disease progress, nearly half (11/25) of the patients accepted second line treatment, 3 had pembrolizumab, 3 enrolled in clinical trials, and others accepted chemotherapy or antiangiogenesis drugs. The ORR of second line was 14.3% (2/14) and median PFS was 5.1m(2.2m-8.0m). At the data cutoff of follow-up (July 31, 2020), OS events were 11 (44%), and median OS was 33.9m(3.2m-64.7m). Conclusion: The most common genotype of NSCLC with BRAF mutation was V600E mutation, which was more tendency to have a concomitant mutation, the therapeutic response was well, and overall survival data had showed a promising outcomes.