OS benefit in VIALE-C trial

The extended findings from the phase 3 VIALE-C trial position low-dose cytarabine (LDAC) plus the BCL-2 inhibitor venetoclax "as a potential new standard of care" for untreated acute myeloid leukaemia (AML) patients ineligible for intensive chemotherapy.

Prof. Andrew Wei (Monash University, Australia) presented the updated 18-month findings from the phase 3 VIALE-C AML trial [1]. The 12 month follow-up data were recently published in the journal Blood [2].

In VIALE-C, 211 AML patients were randomised to daily oral venetoclax 600 mg (n=143) or to placebo (n=68) in 28-day cycles, on top of a backbone therapy of LDAC 20 mg/m² administered subcutaneously on days 1-10 of each cycle. The primary endpoint was overall survival (OS). With 18 months of follow-up in treatment-naïve AML patients of 75 years or older or younger adult patients who were otherwise unfit for intensive chemotherapy, the median OS was 8.4 months when they were randomised to LDAC plus venetoclax versus 4.1 months with LDAC plus placebo. The 4.3-month OS benefit with the combination translated into a 30% reduction in the risk of death (HR 0.70; 95% CI, 0.50-0.99; P=0.04). Key secondary outcome measures were also met. The complete remission (CR) rate was 27.3% in the venetoclax arm versus 7.4% in the LDAC arm. The CR with incomplete blood count recovery (CRi) was 47.6% in the venetoclax group compared with 13.2% in the LDAC arm. The CR with partial haematologic recovery was 46.9% in the venetoclax arm versus 14.7% in the LDAC arm. For the final outcome of CR plus CRi by the initiation of cycle 2, the rate observed was 34.3% in the venetoclax group compared with 2.9% in the LDAC group.

The safety profiles of both agents were consistent with previous reports. The most common adverse events observed in the venetoclax and LDAC groups (respectively) were febrile neutropenia (15.5% vs 11.8%), neutropenia (45.8% vs 17.7%), thrombocytopenia (40.9% vs 36.8%), and anaemia (26.1% vs 22.1%).

"This study enrolled a challenging AML population, with nearly 60% aged ≥75 years and a high proportion of patients with secondary disease (38%), prior hypomethylating agent (HMA) treatment (20%), poor cytogenetic risk (32%), and TP53 mutations (15%), which are known factors associated with dismal prognosis in AML”, said Prof. Wei.

1. 
   
   1. Wei AH, et al. A phase 3 study of venetoclax plus low-dose cytarabine in previously untreated older patients with acute myeloid leukemia (VIALE-C): a 6-month update. EHA25 Virtual, 11-21 June 2020, Abstract S136.
   2. Wei AH, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020;135(24):2137-2145.

Posted on 9 September 202029 February 2024