On November 21, 2018, the United States Food & Drug Administration(FDA) granted accelerated approval to venetoclax in combination with azacitidine, decitabine or low-dose cytarabine (LDAC) for patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive induction therapy due to older age (≥ 75 years) or coexisting medical conditions. This decision was dependent upon the confirmatory phase III clinical trials, VIALE-A and VIALE-C. 1
It has been announced that the VIALE-A trial ( NCT02993523), comparing venetoclax plus azacitidine to placebo plus azacitidine, has met the dual primary endpoints, with the combination therapy leading to a significant improvement in overall survival (OS) and composite complete remission rate. 2
- Phase III, randomized, double-blind, placebo-controlled, multicenter study
Patients with previously untreated AML who were ineligible for intensive induction chemotherapy (n = 431) were randomized 2:1 to
- venetoclax (400 mg, orally, once daily on Days 1–28) + azacitidine (75 mg/m 2, subcutaneously [SC] or intravenously [IV], once daily on Days 1–7)
- placebo (orally, as per venetoclax dosing schedule) + azacitidine (as above)
Patients were defined as ineligible for intensive induction chemotherapy due to
- age≥ 75 years
- comorbidities that are incompatible with intensive chemotherapy
- Primary endpoints: OS and composite complete remission rate (complete response [CR] plus CR with incomplete blood count recovery)
- Secondary endpoints: event-free survival, CR and CR with partial hematologic recovery, transfusion independence, and patient reported outcomes
In February 2020, it was announced that the phase III VIALE-C trial ( NCT03069352), comparing venetoclax plus LDAC to placebo plus LDAC, failed to meet the primary endpointof a significant improvement in OS in patients with newly diagnosed AML who are ineligible for intensive induction chemotherapy.
The full results from VIALE-A and VIALE-C are expected to be presented at an upcoming medical congress. The FDA has not yet commented about whether the results of the VIALE-A or VIALE-C trial will impact the current approval. 1
The AML Hubare currently focusing on an editorial theme of ‘novel combination therapies using targeted agents’. Venetoclax is a targeted agent that inhibits Bcl-2 and is under investigation in various combination therapies, such as with the hypomethylating agents azacitidine and decitabine, as discussed here. To learn more about targeted agent combinations in AML, click here.