Molecular and immune profiling of BRAF -mutated ( BRAF MUT ) non-small cell lung cancer (NSCLC).

作者：Roupen Odabashian, S Wang, N. Gandhi, Biagio Ricciuti, Alessandro Di Federico, Hossein Borghaei, Balazs Halmos, Hirva Mamdani · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco.2026.44.16_suppl.8653 · 研究领域：Melanoma and MAPK Pathways、Lung Cancer Treatments and Mutations、Cancer Immunotherapy and Biomarkers

8653 Background: BRAF MUT occur in 6-7% of NSCLC and comprise of biologically distinct classes showing variable therapeutic responses. While Class 1 benefits from targeted therapy, molecular and immune determinants distinguishing BRAF classes remain incompletely characterized. We performed comprehensive profiling to identify class-specific biomarkers. Methods: 51,692 (BRAF wild-type [ BRAF WT ]: n=48,288; BRAF MUT : n=3404) NSCLC specimens underwent DNA (592-gene panel/whole-exome) and/or RNA (whole-transcriptome) sequencing at Caris Life Sciences. BRAF MUT tumors were classified into 3 Classes, other pathogenic variants (O PV ), and unknown/unclassified variants (VUS). The tumor microenvironment (TME) was estimated using the QuanTIseq method. Overall survival (OS) and IO-associated survival (IO-OS) were derived from insurance claims and calculated from the date of tumor biopsy (OS) or IO initiation (IO-OS) to last contact using Kaplan-Meier estimates. Statistical significance was determined by Fisher’s Exact, chi-square, and Mann-Whitney U test with adjustments for multiple comparisons ( P <0.05). Results: Class 1 was significantly enriched for SETD2 mutations (mut) and more frequently PDL1+ (22c3, TPS>=1) while showing a lower prevalence of TMB-high (>=10 mut/Mb), TP53, STK11 and KEAP1 mut (Table). Class 2/3 tumors were moderately PDL1+ and TMB-high and enriched for STK11 and KEAP1 muts (Table). While both OPV and VUS were enriched for TMB-high and not PDL1, OPV wa...