Venetoclax plus low-dose cytarabine offers a clinically meaningful improvement in survival compared with placebo plus low-dose cytarabine in previously untreated older patients with acute myeloid leukemia (AML), according to results of a phase III study (VIALE-C) to be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting (May 29-31, 2020).
VIALE-C was a double-blind, phase III study designed to compare the safety and efficacy of venetoclax or placebo plus low-dose cytarabine in previously untreated patients with AML aged at least 75 years or at least 18 years with comorbidities precluding intensive chemotherapy. The initial overall survival (OS) analysis showed a clinically meaningful improvement in the venetoclax arm, though the primary endpoint end point was not met.
Andrew H Wei, MBBS, FRACP, FRCPA, PhD, The Alfred Hospital and Monash University (Melbourne, Australia), and colleagues provided a 6-month update after the primary analysis, with a focus on OS. As of August 15, 2019, a total of 211 patients were randomized – 143 of whom to the venetoclax arm and 68 of whom to the placebo arm. The median patient age was 76 years in both arms (range, 36 to 93 years).
After a median follow-up of 17.5 months, the median OS was 8.4 months in the venetoclax arm and 4.1 months in the placebo arm (HR, 0.70; 95% CI, 0.50-0.99; P = .04), which represented a 30% reduction in the risk of death. Researchers also found that complete remission and complete remission with partial hematologic recovery rates were both 48% for the venetoclax arm and 13% and 15%, respectively, for the placebo arm.
Additionally, Dr Wei and colleagues reported that median event-free survival was 4.9 vs 2.1 months, respectively, for the venetoclax and placebo arms (HR, 0.61; 95% CI, 0.44-0.84;
P = .003).
Grade 3 adverse events included neutropenia (49% vs 18%, respectively), thrombocytopenia (45% vs 38%, respectively), and febrile neutropenia (32% vs 29%, respectively).
In their concluding remarks, authors of the study noted that venetoclax plus low-dose cytarabine demonstrated a clinically meaningful improvement in OS compared with placebo plus low-dose cytarabine, with a tolerable and manageable safety profile. "These data support venetoclax plus low-dose cytarabine as a frontline treatment option for older patients with AML, as well as those considered unfit for intensive chemotherapy," they wrote.—Zachary Bessette
