Sunitinib in Patients with Metastatic Colorectal Cancer (mCRC) with FLT-3 Amplification: 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 of FMS - like tyrosine kinase - 3 (...

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Published in:Targeted oncology 2020-12, Vol.15 (6), p.743-750
Main Authors: Al Baghdadi, Tareq, Garrett-Mayer, Elizabeth, Halabi, Susan, Mangat, Pam K., Rich, Patricia, Ahn, Eugene R., Chai, Seungjean, Rygiel, Andrew L., Osayameh, Olufunlayo, Antonelli, Kaitlyn R., Islam, Samiha, Bruinooge, Suanna S., Schilsky, Richard L.
Format: Article
Language:English
Subjects:
Adult
Aged
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Biomedicine
Cancer therapies
Clinical trials
Colorectal cancer
Colorectal Neoplasms - drug therapy
Drug dosages
FDA approval
Female
fms-Like Tyrosine Kinase 3 - metabolism
Humans
Inhibitor drugs
Kinases
Laboratories
Male
Medical research
Medicine
Medicine & Public Health
Metastasis
Middle Aged
Mutation
Oncology
Original Research Article
Patients
Registries
Sunitinib - pharmacology
Sunitinib - therapeutic use
Targeted cancer therapy
Tumors
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Summary: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 of FMS - like tyrosine kinase - 3 ( FLT - 3 ), among other targets. Results from a cohort of patients with metastatic colorectal cancer (mCRC) with FLT - 3 amplification treated with sunitinib are reported. Objective This study aimed to investigate whether patients with mCRC with FLT - 3 amplification 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 with FLT - 3 amplification. 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 with FLT - 3 amplification and should not be prescribed for off-label use. Other treatments should be considered for these patients, including treatments offered in clinical trials. Clinical Trial registration NCT02693535 (26 February 2016).
ISSN:1776-2596
1776-260X
DOI:10.1007/s11523-020-00752-8