New safe and effective treatments are urgently needed for patients with relapsed or refractory (RR) acute myeloid leukemia (AML). Vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine has been previously investigated in a phase 1/2 trial in patients (n = 69) with first relapsed or primary refractory AML [Lancet JE et al. Haematologica. 2014]. Median overall survival (OS) was 6.9 months, the complete remission (CR) rate was 25%, the median leukemia-free survival (LFS) was 25.2 months, and 60-day all-cause mortality was 8.7%.

Farhad Ravandi, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, USA, presented results of the Study of Vosaroxin or Placebo in Combination With Cytarabine in Patients With First Relapsed or Refractory Acute Myeloid Leukemia [VALOR; Ravandi F et al. ASH 2014 (abstr LBA-6)]. VALOR was a phase 3, double-blind, randomized, placebo-controlled study. Patients with first RR AML were randomly assigned to vosaroxin (n = 356) 90 mg/m² days 1 and 4 of the first cycle and 70 mg/m² for the second cycle plus cytarabine 1 g/m² days 1 through 5 or to placebo (n = 355) days 1 and 4 plus cytarabine for 1 to 2 cycles of induction.

If the response was CR or complete remission with incomplete platelet recovery (CRp) patients received consolidation with 1 to 2 cycles. For complete remission with insufficient hematologic recovery (CRi), partial remission (PR), or treatment failure, there was no further treatment. The primary end point was OS; secondary end points were CR, safety, and tolerability. Tertiary end points included CR + CRp + CRi, event-free survival (EFS), LFS, and stem cell transplant (SCT) rate.

Patients in both groups were well matched for characteristics. The median age was 63 years; 42% had refractory AML, 36% were in early relapse, and 22% were in late relapse.

OS was 7.5 months for the combination vs 6.1 months for cytarabine monotherapy (P = .06; HR 0.87; 95% CI, 0.73 to 1.02); by stratified log-rank analysis P = .02. CR rates are shown in Table 1, and rates of CR + CRp + CRi are shown in Table 2.

Overall, 30.1% of patients in the combination group had allogeneic SCT vs 29% in the placebo group. The percentages of patients aged < 60 years receiving SCT were higher (46.2% vs 45.4% for the combination and control arms, respectively) than those of patients aged ≥ 60 years (20.8% vs 19.6% for the combination and control arms, respectively). A higher proportion of patients in the vosaroxin arm underwent an allogeneic SCT after achieving CR on the initial prescribed therapy. In a preplanned analysis of OS censored for allogeneic SCT, OS in the vosaroxin arm was a median 6.7 months vs 5.3 months in the placebo arm (HR, 0.83; P = .02). In an analysis of OS by subgroup, the vosaroxin combination was favored in patients aged ≥ 60 years and with early relapse. EFS was significantly better for patients treated with vosaroxin and cytarabine (P < .0001). LFS was not significantly different between groups.

The clinical benefit of vosaroxin combination therapy may be underestimated in younger patients due to the high rate of SCT. All-cause mortality was similar for both groups at 30 and 60 days. The most common serious adverse events were febrile neutropenia, sepsis, pneumonia, bacteremia, and stomatitis, and were higher in the vosaroxin group but these did not translate to excess mortality. Serious and nonserious cardiac, renal, neurologic, and hepatic adverse events were comparable between treatment groups. Vosaroxin plus cytarabine provides patients with relapsed, refractory AML with a new option for salvage therapy.