SAN FRANCISCO – Adding a kinase inhibitor to a standard regimen for acute myeloid leukemia can prolong event-free and relapse-free survival in young adult patients, but the effect on overall survival is still unclear, investigators reported.
In a randomized controlled trial, 3-year event-free survival (EFS), the primary endpoint, was 40% among patients treated with chemotherapy and sorafenib (Nexavar), compared with 22% for patients treated with chemotherapy and a placebo (P = .013). The median EFS was 21 months and 9 months, respectively, reported Dr. Christoph Röllig of University Hospital in Dresden, Germany.
Dr. Christoph Röllig
Relapse-free survival (RFS) at 3 years was 56% in the sorafenib-treated group, compared with 38% in the placebo group (P = .017). The median RFS was not reached in the sorafenib group, vs. 23 months in the placebo group, Dr. Röllig reported at the annual meeting of the American Society of Hematology.
“These data constitute the first randomized evidence that actually kinase inhibitors work in AML. What we judge is that, according to evidence-based medicine principles, a comparatory trial would be desirable in order to establish sorafenib in AML treatment,” he said at a briefing prior to his presentation of the data in a plenary session.
Dr. Röllig and colleagues in 25 centers enrolled patients from 18 to 60 years with newly diagnosed AML. Of the 276 enrolled, 267 went on to receive study treatment: 134 were assigned to sorafenib and 133 to placebo. The study drug was given along a chemotherapy regimen consisting of two cycles of induction with daunorubicin and cytarabine followed by three cycles of high-dose cytarabine consolidation. Patients who did not have a response after the first cycle of daunorubicin induction underwent a second induction attempt with cytarabine and mitoxantrone.
The assigned study medication was given on days 10-19 of induction cycles one and two, from day 8 of each consolidation cycle until 3 days before the start of the next consolidation cycle, and as maintenance for 12 months after the end of consolidation.
As noted before, EFS in an intention-to-treat analysis censored for stem-cell therapy favored the sorafenib-treated patients, as did RFS. In addition, there was evidence to suggest a benefit trend toward prolonged RFS and overall survival with sorafenib among patients positive for the FLT3-ITD mutation, which has been shown to be sensitive to kinase inhibitors.
Patients in the sorafenib arm had significantly more episodes of fever, bleeding events, and the hand-foot syndrome, but there were no significant differences in other adverse events, Dr. Röllig said.
In an interview, he said that the investigators chose sorafenib because of its good track record and its efficacy against multiple kinases. His center is also involved in clinical trials exploring whether a different kinase inhibitor, quizartinib, has similar or better efficacy against AML.
The study was supported by Bayer. Dr. Röllig reported having no relevant disclosures.