386P - TP53 GOF mutations predict good response and prolonged survival to bevacizumab treatment in metastatic colorectal cancer

Abstract

Background: TP53 mutations have been correlated with improved outcomes in patients treated with anti-angiogenic agents. However, the association between TP53 mutation subtypes and bevacizumab response in colorectal cancer remains to be investigated. Methods: Metastatic colorectal cancer patients (n = 36) treated with bevacizumab were enrolled and subjected to next-generation sequencing (NGS) for TP53 mutation analysis. TP53 mutations such as loop 2 (L2), loop 3 (L3), LSH motif mutations, gain-of-function (GOF) mutations and loss-of-function (LOF) mutations were correlated with the progression-free survival (PFS) and tumor shrinkage. Results: Patients harboring TP53 GOF mutations (n = 13) are associated with better PFS compared with other patients (14.1 versus 9.5 months, p = 0.002), whereas patients with LOF mutations (n = 6) had shorter PFS than the rest of the cohort (5.8 versus 12.7 months, p = 0.002). In addition, more pronounced tumor shrinkage has been observed in TP53 GOF mutations group (p = 0.050). However, there was no association between the carriage of any TP53 mutation (n = 28) or a TP53 L2, L3 or LSH mutation (n = 19) with PFS or tumor shrinkage. Conclusions: TP53 mutation subtypes confer different therapeutic outcome in metastatic colorectal cancer patients treated with bevacizumab and TP53 GOF mutations are a candidate biomarker for better bevacizumab sensitivity. Legal entity responsible for the study: ACT Genomics. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.