No Difference in Overall Survival With Addition of Quinolone Derivative Vosaroxin to Cytarabine in Relapsed or Refractory AML


Key Points

  • No significant difference in overall survival was observed in the primary analysis of the phase III VALOR trial.
  • Significant benefit favoring vosaroxin was observed in stratified analysis, analysis censoring for subsequent transplantation, and in patients aged ≥ 60 years and those with early relapse on prior therapy.

In a phase III VALOR trial reported in The Lancet Oncology, Ravandi et al found that the addition of the quinolone derivative vosaroxin to cytarabine did not significantly improve overall survival in patients with relapsed or refractory acute myeloid leukemia (AML). However, differences favoring vosaroxin vs placebo were observed in analysis by stratification factors, a sensitivity analysis censoring for subsequent allogeneic stem cell transplantation, and in patients aged ≥ 60 years and those with early relapse on prior therapy.

Study Details

In this double-blind trial, 711 adult patients from 101 international sites were randomly assigned between December 2010 and September 2013 to receive vosaroxin 90 mg/m2 intravenously on days 1 and 4 in a first cycle and 70 mg/m2 in subsequent cycles plus cytarabine 1 g/m2 intravenously on days 1 to 5 (n = 356) or placebo plus cytarabine (n = 355). A second induction cycle could be started between 14 days and 8 weeks after the start of cycle 1 at the discretion of the investigator.

All patients had refractory disease or were in first relapse after one or two cycles of previous induction therapy, including at least one cycle of anthracycline (or anthracenedione) plus cytarabine. Randomization was stratified by disease status, age, and geographic location. The primary endpoint was overall survival on intent-to-treat analysis.

Overall Survival Outcomes

Median follow-up was 24.4 months. Median overall survival was 7.5 months (95% confidence interval [CI] = 6.4–8.5 months) in the vosaroxin group vs 6.1 months (95% CI = 5.2–7.1 months) in the placebo group; the hazard ratio (HR) of 0.87 was not significant on unstratified analysis (P = .061) but was significant on stratified analysis (P = .024). In a predefined analysis censoring for subsequent allogeneic stem cell transplantation, median overall survival was 6.7 months vs 5.3 months (HR = 0.81, P = .024).

Subgroup analyses suggested a survival benefit of vosaroxin among patients aged ≥ 60 years (median 7.1 vs 5.0 months, HR = 0.75, P = .0030) and in those with early relapse on prior therapy (median 6.7 vs 5.2 months, HR = 0.77, P = .039). Complete remission was achieved in 30% vs 16% of patients (P < .0001).

Early Mortality and Adverse Events

Thirty-day (8% vs 7%) and 60-day mortality (20% vs 19%) were similar in the two groups. Treatment-related death occurred at any time in 6% vs 2% of patients. Treatment-related serious adverse events occurred in 33% vs 17%. Grade ≥ 3 adverse events that were more frequent in the vosaroxin group included febrile neutropenia (47% vs 33%), neutropenia (19% vs 14%), stomatitis (15% vs 3%), hypokalemia (15% vs 6%), bacteremia (12% vs 5%), sepsis (12% vs 5%), and pneumonia (11% vs 7%).

The investigators concluded: “Although there was no significant difference in the primary endpoint between groups, the prespecified secondary analysis stratified by randomisation factors suggests that the addition of vosaroxin to cytarabine might be of clinical benefit to some patients with relapsed or refractory acute myeloid leukaemia.”

Farhad Ravandi, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author of The Lancet Oncology article.

The study was funded by Sunesis Pharmaceuticals. For full disclosures of the study authors, visit

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