Cabozantinib May Be Effective for Acute Myeloid Leukemia

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Standard cytotoxic chemotherapy remains the standard treatment for AML, though a large proportion of patients relapse and/or develop resistance to conventional therapy, indicating a need for new treat
Standard cytotoxic chemotherapy remains the standard treatment for AML, though a large proportion of patients relapse and/or develop resistance to conventional therapy, indicating a need for new treat

Cabozantinib may help to evade drug resistance in patients with acute myeloid leukemia (AML), according to research published in Cancer.1

Standard cytotoxic chemotherapy remains the standard treatment for AML, though a large proportion of patients relapse and/or develop resistance to conventional therapy, indicating a need for new treatments. FLT3 mutations are, furthermore, associated with a worse prognosis, and while novel FLT3 inhibitors can be effective in AML, resistance to targeted therapy tends to evolve.

For this phase 1, dose-escalation study (ClinicalTrials.gov Identifier: NCT01961765), researchers evaluated the efficacy and toxicity of cabozantinib, a multi-kinase inhibitor of FLT3, MET, VEGFR2, and KIT, among patients with AML. Of 18 enrolled patients, the median age was 68, 16 had relapsed/refractory disease, 2 had newly diagnosed disease, and 5 had detectable FLT3 mutations.

The maximum tolerated dose was determined to be 40 mg, notably lower than for other cabozantinib indications, as dose-limited toxicities were observed with the 60 mg dose.

No formal marrow responses were observed and the median overall survival was 3.88 months.

The researchers observed, however, that 4 patients “had a reduction in peripheral blasts during treatment, and 2 of these patients transiently cleared their circulating blasts (1 with an FLT3/ITD mutation).”

Grade 2 or worse toxicities that may have been related to the experimental treatment included fatigue, nausea, transaminitis, and electrolyte imbalance.

The authors concluded that “cabozantinib…effectively inhibits the FLT3/TKD/F691 resistance mutation and may, therefore, play a role in future therapeutic paradigms.”

Reference

  1. Fathi AT, Blonquist TM, Hernandez D, et al. Cabozantinib is well tolerated in acute myeloid leukemia and effectively inhibits the resistance-conferring FLT3/tyrosine kinase domain/F691 mutation. Cancer. 2017 Sep 28. doi: 10.1002/cncr.31038 [Epub ahead of print]

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