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Novel PLK1 Inhibitor Plus Decitabine or Cytarabine Under Study in Resistant AML

By: Kayci Reyer
Posted: Monday, December 14, 2020

According to early findings published in Clinical Cancer Research, a combination treatment of the Polo-like kinase 1 (PLK1) inhibitor onvansertib plus decitabine may be well tolerated and might result in antileukemic activity in some patients with acute myeloid leukemia (AML). Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, and colleagues sought to determine the dose-limiting toxicities and maximum tolerated dose of this combination therapy versus onvansertib plus low-dose cytarabine in patients with relapsed or refractory disease.

“Results of this phase Ib study justify further investigation of the onvansertib and decitabine combination in patients with relapsed or refractory AML,” the authors commented. “The identification of predictive biomarkers would be key to enrich for patients who are likely to benefit from the onvansertib and decitabine combination.”

The phase Ib study included 40 patients who received escalating doses of oral onvansertib (12–90 mg/m2) on days 1 to 5 of a 28-day cycle. It was administered in combination with 20 mg/m2 of low-dose cytarabine on days 1 to 10 for 17 patients and 20 mg/m2 of decitabine on days 1 to 5 for 23 patients. In the decitabine group, where the maximum tolerated dose of onvansertib was determined to be 60 mg/m2, 5 of the 21 evaluable patients (24%) achieved complete remission with or without hematologic count recovery.

An association was noted between the achievement of clinical response and a decline in mutant circulating tumor DNA within the initial treatment cycle. A relationship was also observed between a decrease in bone marrow blasts and engagement of TCTP, the PLK1 target as measured in circulating blasts. The majority of grade 3 or 4 adverse events related to onvansertib were associated with myelosuppression. Overall, the treatment was reported to be well tolerated.

Disclosure: For full disclosures of the study authors, visit clincancerres.aacrjournals.org.


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