In a phase 3 trial, adding the quinolone derivative vosaroxin (Qinprezo) to treatment with cytarabine did not improve overall survival in patients with relapsed or refractory acute myeloid leukemia (AML).
However, the combination did confer a survival benefit when transplant patients were excluded from the analysis and in patients age 60 and older.
Results of this trial were recently announced by Sunesis Pharmaceuticals, the company developing vosaroxin.
The results are set to be presented in more detail at an upcoming scientific conference.
The trial, known as VALOR, enrolled 711 AML patients who had relapsed or become refractory to treatment for the first time. The patients were randomized to receive cytarabine plus vosaroxin or cytarabine plus placebo. They were stratified for age, geography, and disease status.
The trial did not meet its primary endpoint of demonstrating a significant improvement in overall survival. The median overall survival was 7.5 months in the vosaroxin-cytarabine arm and 6.1 months in the placebo-cytarabine arm (hazard ratio [HR]=0.865, P=0.06).
However, there was a significant benefit in complete response rate with vosaroxin over placebo—30.1% and 16.3%, respectively (P=0.0000148).
Because transplant could confound the primary analysis, the researchers planned a predefined analysis of overall survival censoring for stem cell transplant.
In this analysis, patients receiving the vosaroxin combination had a median overall survival of 6.7 months, compared to 5.3 months for placebo and cytarabine (HR=0.809, P=0.02).
Results according to age
For age, the researchers stratified patients into those age 60 years and older and those younger than 60 years at enrollment.
For the younger patients (n=260), the median overall survival was 9.1 months in the vosaroxin-cytarabine arm and 7.9 months in the placebo-cytarabine arm (HR=1.079, not significant).
The complete response rates were 26.9% and 20.8%, respectively (P=0.24). The rate of stem cell transplant was 45.8% in this age group.
For patients aged 60 years and older (n=451), the median overall survival was 7.1 months in the vosaroxin-cytarabine arm and 5.0 months in the placebo-cytarabine arm (HR=0.755, P=0.006).
The complete response rates were 31.9% and 13.8%, respectively (P=0.0000048). The rate of stem cell transplant was 20.2% for this age group.
Adverse events and mortality
In the intent-to-treat population, grade 3 or higher non-hematologic adverse events that were more common in the vosaroxin arm were gastrointestinal and infection-related toxicities. This is consistent with events observed in previous company trials.
The rate of serious adverse events was 55.5% in the vosaroxin-cytarabine arm and 35.7% in the placebo-cytarabine arm.
All-cause mortality rates were similar between the arms. Thirty-day mortality rates were 7.9% in the vosaroxin-cytarabine arm and 6.6% in the placebo-cytarabine arm. And 60-day mortality rates were 19.7% and 19.4%, respectively.
Regulatory plans
Based on the results of the trial, Sunesis plans to submit a marketing authorization application for vosaroxin to the European Medicines Agency. The company also plans to meet with the US Food and Drug Administration (FDA) to determine the appropriate regulatory path forward.
The FDA and the European Commission have already granted orphan designation to vosaroxin for the treatment of AML. The drug has been granted fast track designation by the FDA as well, for the potential treatment of relapsed or refractory AML in combination with cytarabine.
