TP53 DNA Binding Domain Mutations Predict Progression-Free Survival of Bevacizumab Therapy in Metastatic Colorectal Cancer

Cancers
Hung-Chih HsuKien Thiam Tan

Abstract

(1) Background: Bevacizumab-based regimens are a standard treatment for metastatic colorectal cancer (mCRC) patients, however meaningful clinical biomarkers for treatment benefit remain scarce. (2) Methods: Tumor samples from 36 mCRC patients treated with bevacizumab-based chemotherapy underwent comprehensive genomic profiling. Alterations in frequently altered genes and important signaling pathways were correlated with progression-free survival (PFS). (3) Results: Overall genetic alteration analysis of investigated genes and pathways did not identify promising new predictors of PFS. However, when considering mutation subtypes, TP53 DNA binding domain (DBD) missense mutations were associated with prolonged PFS (HR, 0.41; 95% CI, 0.13-0.65; p = 0.005). In contrast, TP53 truncating mutations were associated with short PFS (HR, 2.95; 95% CI, 1.45-27.50; p = 0.017). Importantly, neither TP53 mutation subtype was associated with overall response rate. In multivariate analysis, TP53 DBD missense mutations remained an independent PFS predictor (HR, 0.31; 95% CI, 0.13-0.77; p = 0.011). The other genetic factor independently associated with PFS were PTPRT/PTPRD deleterious alterations, which we previously identified in a screen for biom...Continue Reading

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