FDA Grants Full Approval to Venetoclax Combo in Newly Diagnosed AML

The FDA has granted regular approval to venetoclax (Venclexta) in combination with azacitidine, decitabine, or low-dose cytarabine (LDAC) for patients with newly diagnosed acute myeloid leukemia (AML) who are 75 years or older or who have comorbidities precluding intensive induction chemotherapy.

The agent received prior approval for this indication in November 2018. The efficacy of venetoclax was confirmed in 2 randomized, double-blind, placebo-controlled trials in this patient population: VIALE-A (NCT02993523) and VIALE-C (NCT03069352).

In VIALE-A, patients were randomized to receive either venetoclax in combination with azacitidine (n = 286) or placebo plus azacitidine (n = 145). Results showed an improvement in overall survival (OS) with venetoclax.

Specifically, the median OS was 14.7 months (95% CI, 11.9-18.7) in those who received venetoclax/azacitidine versus 9.6 months (95% CI, 7.4-12.7) in those who were given placebo/azacitidine (HR 0.66; 95% CI, 0.52-0.85; P <0.001). Patients who received the venetoclax combination also showed an improvement in complete remission (CR) rate versus the placebo, at 37% (95% CI, 31%-43%) versus 18% (95% CI, 12%-25%), respectively.

In VIALE-C, patients were randomized to receive either venetoclax in combination with LDAC (n = 143) or placebo plus LDAC (n = 68). Results showed that the CR rate with venetoclax/LDAC was 27% (95% CI, 20%-35%) versus 7.4% (95% CI, 2.4%-16%) with placebo/LDAC. Moreover, the median duration of response was 11.1 months in the investigational arm (95% CI, 6.1–not reached [NR]) versus 8.3 months in the control arm (95% CI, 3.1-NR; HR, 0.75; 95% CI, 0.52-1.07; P =.114).

With regard to safety, the most frequently experienced toxicities with the venetoclax combination include nausea, diarrhea, thrombocytopenia, constipation, neutropenia, febrile neutropenia, and fatigue. Other adverse effects include vomiting, edema, pyrexia, pneumonia, dyspnea, hemorrhage, anemia, rash, abdominal pain, sepsis, musculoskeletal pain, dizziness, cough, oropharyngeal pain, and hypotension.

Reference

FDA grants regular approval to venetoclax in combination for untreated acute myeloid leukemia. News release. October 16, 2020. Accessed October 16, 2020. https://bit.ly/2Hgqoos.