March 02, 2020
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Venetoclax regimen fails to extend OS in newly diagnosed AML

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A randomized phase 3 study designed to evaluate the addition of venetoclax to low-dose cytarabine failed to show significant OS improvement among patients with newly diagnosed acute myeloid leukemia who were ineligible for intensive chemotherapy, according to the agent’s manufacturer.

Venetoclax (Venclexta; AbbVie, Genentech) selectively binds and inhibits the BCL-2 protein.

The agent is approved in the United States as monotherapy for adults with chronic lymphocytic leukemia or small lymphocytic lymphoma. It also is approved in combination with azacitidine, decitabine or low-dose cytarabine to treat adults with newly diagnosed AML who are aged 75 years or older or have other medical conditions that prevent the use of standard chemotherapy.

The double-blind, placebo-controlled VIALE-C trial included a broader population of patients with treatment-naive AML.

The study included 211 patients aged 18 years or older who received venetoclax plus low-dose cytarabine (n = 143) or placebo plus low-dose cytarabine (n = 68).

OS served as the primary endpoint.

Patients assigned the venetoclax regimen achieved numerically longer median OS, but the difference did not reach statistical significance (7.2 months vs. 4.1 months; HR = 0.75; 95% CI, 0.52-1.07).

A post-hoc analysis after another 6 months of follow-up showed median OS of 8.4 months with the venetoclax regimen and 4.1 months with low-dose cytarabine alone (HR = 0.7; 95% CI, 0.5-0.99).

An analysis of select secondary endpoints showed results favored the venetoclax group with regard to rates of complete remission (27.3% vs. 7.4%), complete remission or complete remission with incomplete blood count recovery (47.6% vs. 13.2%), and complete remission or complete remission with partial hematologic recovery (46.9% vs. 14.7%).

“We remain committed to [patients with AML] and our research in AML and other blood cancers,” Neil Gallagher, MD, PhD, chief medical officer and vice president of development at AbbVie, said in a company-issued press release. “The study results, [although] not statistically significant, are indicative of the clinical activity of venetoclax in combination with low-dose cytarabine.”

The safety profile of venetoclax plus low-dose cytarabine appeared consistent with those of the phase 1/phase 2 studies that supported FDA approval of the combination.

Patients assigned venetoclax appeared more likely to develop febrile neutropenia (nonserious, 15.5% vs. 11.8%; serious, 16.9% vs. 17.7%), neutropenia (nonserious, 45.8% vs. 17.7%; serious, 2.8% vs. 0%), thrombocytopenia (nonserious, 40.9% vs. 36.8%; serious, 4.9% vs. 2.9%) and anemia (nonserious, 26.1% vs. 22.1%; serious, 2.8% vs. 0%).

Complete results will be submitted for publication in a peer-reviewed journal or presentation at a medical meeting.

The phase 3 VIALE-A trial — designed to evaluate venetoclax in combination with azacitidine — is ongoing.