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

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Abstract

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).

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Authors and Affiliations

  1. Michigan Cancer Research Consortium, Ypsilanti, MI, USA

    Tareq Al Baghdadi

  2. American Society of Clinical Oncology, 2318 Mill Road, Alexandria, VA, 22314, USA

    Elizabeth Garrett-Mayer, Pam K. Mangat, Andrew L. Rygiel, Olufunlayo Osayameh, Kaitlyn R. Antonelli, Samiha Islam, Suanna S. Bruinooge & Richard L. Schilsky

  3. Duke University Medical Center, Durham, NC, USA

    Susan Halabi

  4. Cancer Treatment Centers of America, Atlanta, GA, USA

    Patricia Rich

  5. Cancer Treatment Centers of America Chicago, Chicago, IL, USA

    Eugene R. Ahn

  6. Levine Cancer Institute, Atrium Health, Charlotte, NC, USA

    Seungjean Chai

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  1. Tareq Al Baghdadi
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Corresponding author

Correspondence to Pam K. Mangat.

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Funding

Sunitinib (Sutent) and funding for this study were provided by Pfizer, Inc. Additional funding was provided by AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Genentech, and Merck.

Conflict of interest

ASCO receives research support for the TAPUR Study from the following companies: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Genentech, Eli Lilly, Merck, and Pfizer. Susan Halabi, PhD, receives partial grant support from ASCO TAPUR. Seungjean Chai, MD, has participated in a consulting day with Cardinal Health. Tareq Al Baghdadi, MD; Elizabeth Garrett-Mayer, PhD; Pam K. Mangat, MS; Patricia Rich, MD; Eugene R. Ahn, MD; Andrew L. Rygiel, MPH; Olufunlayo Osayameh, MPH; Kaitlyn R. Antonelli; Samiha Islam; Suanna S. Bruinooge, MPH; and Richard L. Schilsky, MD have no conflicts of interest that are directly relevant to the content of this article.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. The study protocol was reviewed and approved by a central institutional review board and, in some cases, by a local institutional review board at participating sites.

Consent to participate

Patients provided written consent before engaging in study-related activities or providing study data and signed informed consent regarding publication of their data.

Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

Author contributions

TAB, EG-M, PKM, SSB, and RLS contributed to the conception and design of this manuscript. TAB, PR, ERA, and SC provided study materials. EG-M, PKM, ALR, OO, KRA, and SI collected and/or assembled data. TAB, EG-M, PKM, ALR, and RLS analyzed and interpreted the data. TAB, PR, EG-M, SH, PKM, OO, KRA, and RLS contributed to the writing and/or revision of the manuscript. All authors read and approved the final manuscript.

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Al Baghdadi, T., Garrett-Mayer, E., Halabi, S. et al. Sunitinib in Patients with Metastatic Colorectal Cancer (mCRC) with FLT-3 Amplification: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. Targ Oncol 15, 743–750 (2020). https://doi.org/10.1007/s11523-020-00752-8

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