Association between tumor mutational burden (TMB) and mutational profile and its effect on overall survival: A post hoc analysis of patients with TMB-high and TMB-low metastatic cancer treated with immune checkpoint inhibitors (ICI).

• DOI: 10.1200/jco.2022.40.16_suppl.2632
• Publication Date: 2022-06-06T16:07:10Z
• Authors: Camila Bragança X...; Gabriela Guardia; Carlos Diego Hola...; Beatriz Mendes Awni; Eduardo Felicio C...; João Pedro Alves; Anamaria Aranha C...; Pedro Alexandre F...; Denis L. Jardim
• Keywords: Microsatellite Instability; STK11

2632 Background: High-TMB was recently approved as an agnostic biomarker for pembrolizumab in advanced cancers. Still, several patients with high-TMB do not respond to ICI, while some low-TMB benefit from immunotherapy. Methods: We collected genomic (MSK-IMPACTassay) and survival data 1,661 assessed OS (Kaplan-Meier method) according the mutational status. To better qualify TMB ≥ 10 mut/Mb (TMB-H) (N = 488, 29%) < (TMB-L) 1,173, 71%) ICI treatment, we analyzed single gene alterations impacting (P 0.05). For all genes exhibiting a correlation OS, conducted Cox multivariate analysis stratified by median TMB, sex, age, microsatellite instability (MSI) status, histology. Results: Survival increased higher TMB. Median 42 15 months TMB-H TMB-L 0.05), respectively. tumors, 5 ( STK11, KEAP1, CIC, E2F3, TP53) exhibited reduced on 22 NTRK3, TERT, NOTCH3, RNF43, TET1, PTPRD, NCOA3, TENT5C, ZFHX3, RIT1, CCNE1, PPM1D, GATA2, ALK, DNMT1, PTPRT, MET, EPHA7, BCL6, SMO, CDK6, MED12) were associated P 0.05. confirmed between mutations STK11 E2F3 worse NTRK, ZFHX3 Histology did play relevant role response except melanoma (better OS; MSI status significantly affect OS. 20 related TP53, H3C2, DAXX, SMARC4, SOX17, RB1, PIK3CA, CTNNB1, KMT2D, HLA-A, FBXW7, CDH1, RBM10, IGF1R, H3C11, EGFR, RUNX1, B2M), 8 VHL, SETD2, PBRM1, BRAF, KDM5C, MAP2K1, CSF1R, RET), superior VHL) inferior H3C1, PIK3CA , In context, histology (except among VHL-mutated tumors) independently Conclusions: This pan-cancer demonstrates that cancer can help define outcomes of treated ICI. [Table: see text]