Sorafenib Failed to Improve EFS in FLT3-ITD AML

The addition of sorafenib to chemotherapy did not prolong event-free survival (EFS) or overall survival (OS) among patients newly diagnosed with acute myeloid leukemia (AML) with a FLT3 internal tandem duplication (FLT3-ITD), according to the results of a phase 2 study published in the journal Blood.

The study randomly assigned 102 adult patients with FLT3-ITD 2:1 to receive sorafenib or placebo in combination with intensive chemotherapy induction comprising idarubicin and cytarabine. All patients were then treated with up to 2 cycles of consolidative chemotherapy and up to 12 cycles of maintenance therapy. The primary endpoint was EFS and secondary endpoints included response rates, OS, and safety. The median follow-up was 49.1 months.

At baseline, the median age was 50 and 59% of patients were female. Nearly all patients had de novo AML with intermediate cytogenetic risk. The median FLT3-ITD allelic ratio was 0.49 and the median length was 44.3 base pairs.

EFS was similar between the groups, with 2-year rates of 47.9% with sorafenib and 45.4% with placebo (hazard ratio [HR], 0.87; 95% CI, 0.51-1.51; P =.61). The 2-year OS was 67% and 58% in the sorafenib and placebo groups, respectively (HR, 0.76; 95% CI, 0.42-1.39).

The response rate was also similar between groups, with an overall response rate of 88% with sorafenib and 94% with placebo. There were 78% of patients in the sorafenib arm who achieved complete remission compared with 70% in the placebo arm. The rates of complete remission with incomplete hematologic recovery were 9% and 24% in the sorafenib and placebo arms, respectively. 

Patients who achieved MRD negativity for FLT3-ITD after induction demonstrated significantly higher 2-year OS of 83% compared with 60% among patients with MRD (HR, 0.40; 95% CI, 0.17-0.93; P =.028). The rate of FLT3-ITD MRD clearance after induction was 44% in the sorafenib arm and 31% in the placebo arm, which increased to 69% and 54%, respectively, after consolidation.

FLT3-ITD negativity “has powerful prognostic utility in deterring survival outcome,” the authors wrote in their report. The rates of grade 3 or higher hematologic and nonhematologic adverse events (AEs) were similar between the groups. The most common grade 3 or higher nonhematologic AE was infection/sepsis in both arms.

“Routine use of pretransplant sorafenib plus chemotherapy in unselected patients with FLT3-ITD AML is not supported by this study,” the authors concluded.

Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Hematology Advisor