The genetic mutation of FMS-like tyrosine kinase 3 (FLT3) was a hot topic at the American Association for Cancer Research (AACR) Annual Meeting 2019.

Several preclinical studies provided more refined and nuanced insights into the target itself, and bioinformatics uncovered a way to measure low levels of residual disease during morphologic remission.1

But some of the most intriguing findings on FLT3 came from two clinical studies with incredibly divergent results.

One was a phase 3 clinical trial, known as the ADMIRAL trial (ClinicalTrials.gov Identifier: NCT02421939), which demonstrated improved overall survival with gilteritinib, a selective inhibitor of FLT3, in patients with FLT3 amplification and relapsed/refractory (R/R) acute myeloid leukemia (AML).2

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The other was a phase 2 trial, called the TAPUR Study (ClinicalTrials.gov Identifier: NCT02693535), in which sunitinib, a multikinase inhibitor, was shown to have insufficient activity as monotherapy in patients with FLT3 amplification and metastatic colorectal cancer (mCRC).3

Principal investigator of the TAPUR Study, Richard L. Schilsky, MD, who is the senior vice president and chief medical officer of the American Society of Clinical Oncology in Alexandria, Virginia, spoke with Cancer Therapy Advisor about the history of FLT3 and the impetus for studying the target in patients with mCRC. “FLT3 mutations have been recognized as an adverse prognostic factor in adults with AML for at least a decade,” he stated. “As a result, these mutations have become targets for cancer treatment.”

He added, “The ASCO TAPUR study seeks evidence of drug efficacy for [U.S. Food and Drug Administration (FDA)]-approved targeted drugs used off-label in tumors with genomic alterations known to be drug targets. Sunitinib, one of the drugs available in the study, targets FLT3 and was used to treat patients with a number of different tumor types with FLT3 mutations or amplification. A cohort of patients with mCRC and FLT3 amplification enrolled a sufficient number of patients for an initial evaluation.”