Identifying predictive biomarkers of apatinib in third-line treatment of advanced colorectal cancer through comprehensive genomic profiling. Issue 3 (18th November 2022)

• Record Type: Journal Article
• Authors: Yang, Dongyang; Xu, Fei; Lai, Xiaorong; Li, Ying; Hou, Ting; Wu, Lihong; Ma, Dong; Li, Zijun
• Is Part Of: Anti-cancer drugs. Volume 34:Issue 3(2023)
• Page Start: 431
• Page End: 438
• Publication Date: 2022-11-18
• Subjects: apatinib -- colorectal cancer -- FLT1 -- next-generation sequencing; Antineoplastic agents -- Periodicals; Cancer -- Chemotherapy -- Periodicals; Antineoplastic Agents -- therapeutic use -- Periodicals; Drug Therapy -- Periodicals; 616.994061
• DOI: 10.1097/CAD.0000000000001451
• Languages: English
• ISSNs: 0959-4973

Abstract

Abstract : Apatinib is a selective inhibitor of vascular endothelial growth factor receptor-2. Despite encouraging anticancer activity in different cancer types, some patients may not benefit from apatinib treatment. Herein, we characterized genomic profiles in colorectal cancer (CRC) patients to explore predictive biomarkers of apatinib at molecular level. We retrospectively recruited 19 CRC patients receiving apatinib as third-line treatment. Tissue samples before apatinib treatment were collected and subjected to genomic profiling using a targeted sequencing panel covering 520 cancer-related genes. After apatinib treatment, the patients achieved an objective response rate of 21% (4/19) and disease control rate of 57.9% (11/19). The median progression-free survival (PFS) and overall survival were 5 and 8.7 months, respectively. Genetic alterations were frequently identified in TP53 (95%), APC (53%), KRAS (53%) and PIK3CA (26%). Higher tumor mutation burden levels were significantly observed in patients harboring alterations in ERBB and RAS signaling pathways. Patients harboring FLT1 amplifications ( n = 3) showed significantly worse PFS than wild-type patients. Our study described molecular profiles in CRC patients receiving apatinib treatment and identified FLT1 amplification as a potential predictive biomarker for poor efficacy of apatinib. Further studies are warranted to validate the use of FLT1 amplification during apatinib treatment.