The addition of sorafenib to standard chemotherapy had antileukemic efficacy but also increased toxicity in patients with acute myeloid leukemia (AML), a new study published online ahead of print in the journal The Lancet Oncology has shown.1

Because preclinical research suggested that sorafenib, a tyrosine kinase inhibitor might be an effective agent for the treatment of AML, researchers sought to evaluate the efficacy and tolerability of sorafenib compared with placebo in combination with standard chemotherapy in patients with AML who were 60 years or younger.

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For the multicenter, double-blind, placebo-controlled, phase 2 trial, researchers enrolled 276 patients aged 18 to 60 years with newly diagnosed, previously untreated AML.

Participants were randomly assigned 1:1 to receive 2 cycles of induction chemotherapy with daunorubicin 60 mg/m2 on days 3 to 5 plus cytarabine 100 mg/m2 on days 1 to 7, followed by 3 cycles of high-dose cytarabine 3 g/m2 consolidation therapy on days 1, 3, and 5 plus sorafenib 400 mg twice daily or placebo on days 10 to 19 of the first 2 induction cycles, from day 8 of each consolidation, and as maintenance for 12 months.

Intermediate-risk patients with a sibling donor and high-risk patients with a matched donor in first remission were scheduled for allogeneic stem-cell transplantation.

Results showed that among the 267 evaluable patients, the median event-free survival was 9 months (95% CI, 4 – 15) in the placebo arm compared with 21 months (95% CI, 9 – 32) in the sorafenib arm. The 3-year event free survival was 22% (95% CI, 13 – 32) and 40% (95% CI, 29 – 51), respectively (HR, 0.64; 95% CI, 0.45 – 0.91; P = .013).

In regard to safety, the most common grade 3 to 4 adverse events in both treatment arms were fever, infections, pneumonia, and pain. Grade 3 or higher fever, diarrhea, bleeding, cardiac events, hand-foot skin reactions, and rash were significantly more common in the sorafenib group than the placebo group.

“Our findings suggest that kinase inhibitors could be a useful addition to curative treatment for acute myeloid leukemia. Overall survival after long-term follow-up and strategies to reduce toxicity are needed to determine the future role of sorafenib in treatment of this disease,” the authors concluded.


  1. Röllig C, Serve H, Hüttmann A, et al. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial [published online ahead of print November 5, 2015]. Lancet Oncol. doi: 10.1016/S1470-2045(15)00362-9.