Sunitinib in Patients with Metastatic Colorectal Cancer (mCRC) withFLT-3Amplification: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study

Background TAPUR is a pragmatic, phase II basket study evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known to be drug targets. Sunitinib is an oral multikinase inhibitor ofFMS-like tyrosine kinase-3(FLT-3), among other targets. Results from a cohort of patients with metastatic colorectal cancer (mCRC) withFLT-3amplification treated with sunitinib are reported. Objective This study aimed to investigate whether patients with mCRC withFLT-3amplification would be responsive to sunitinib, an oral multikinase inhibitor. Methods Eligible patients received a standard sunitinib dose of 50 mg orally for 4 weeks followed by 2 weeks off. Simon's two-stage design was used with the primary study endpoint of objective response (OR) or stable disease (SD) at 16 weeks based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints were progression-free survival, overall survival, and safety. Results Ten patients were enrolled from November 2016 to April 2018. All patients had mCRC withFLT-3amplification. No ORs were observed. Although two patients had SD at 16 weeks, one died because of disease progression shortly thereafter and the cohort was closed. A single grade 3 adverse event of diarrhea was reported as possibly related to sunitinib. Conclusions Monotherapy with sunitinib does not have clinical activity in patients with mCRC withFLT-3amplification and should not be prescribed for off-label use. Other treatments should be considered for these patients, including treatments offered in clinical trials.