On October 16, 2020, the Food and Drug Administration granted regular approval to venetoclax in combination with azacitidine, decitabine, or low-dose cytarabine (LDAC) for newly-diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities precluding intensive induction chemotherapy.
Venetoclax was initially granted accelerated approval for this indication in November 2018.
Efficacy was confirmed in two randomized, double-blind, placebo-controlled trials in patients with AML described above.
In VIALE-A (NCT02993523), patients were randomised to receive venetoclax plus azacitidine (n=286) or placebo plus azacitidine (n=145).
Efficacy was established based on an improvement in overall survival (OS).
The median OS was 14.7 months (95% CI: 11.9, 18.7) in patients treated with venetoclax plus azacitidine compared to 9.6 months (95% CI: 7.4, 12.7) in those receiving placebo plus azacitidine (HR 0.66; 95% CI: 0.52, 0.85; p<0.001).
Patients treated with venetoclax plus azacitidine also demonstrated an improvement in complete remission (CR) rate: 37% (95% CI: 31%, 43%) versus 18% (95% CI: 12%, 25%).
In VIALE-C (NCT03069352), patients were randomised to receive venetoclax plus LDAC (n=143) or placebo plus LDAC (n=68).
Efficacy was based on CR rate and duration of CR.
The CR rate on the venetoclax plus LDAC arm was 27% (95% CI: 20%, 35%) with a median duration of 11.1 months (95% CI: 6.1, not reached) compared to 7.4% (95% CI: 2.4%, 16%) with a median duration of 8.3 months (95% CI: 3.1, not reached) in those receiving placebo plus LDAC.
Venetoclax plus LDAC did not significantly improve OS versus placebo plus LDAC (HR 0.75; 95% CI 0.52, 1.07; p=0.114).
The most common adverse reactions of venetoclax in combination with azacitidine, decitabine, or low-dose cytarabine (≥30% in any trial) were nausea, diarrhea, thrombocytopenia, constipation, neutropenia, febrile neutropenia, fatigue, vomiting, edema, pyrexia, pneumonia, dyspnea, hemorrhage, anemia, rash, abdominal pain, sepsis, musculoskeletal pain, dizziness, cough, oropharyngeal pain, and hypotension.
The recommended venetoclax dose depends upon the combination regimen and is described in prescribing information.
View full prescribing information for VENCLEXTA.