First Randomized Trial to Show Benefit of Tyrosine Kinase Inhibitor in Newly Diagnosed Acute Myeloid Leukemia

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Christoph Röllig, MD

Sorafenib in Acute Myeloid Leukemia

Sorafenib (Nexavar) added to chemotherapy improved event-free survival and relapse-free survival in younger patients with acute myeloid leukemia, according to results of the randomized, controlled phase II SORAML trial.1 However, no significant improvement in overall survival has been seen to date.

“Sorafenib plus chemotherapy is feasible in younger patients with acute myeloid leukemia. The drug achieved significant and relevant event-free survival and relapse-free survival but, interestingly, not overall survival,” said lead author ­Christoph Röllig, MD, University Hospital Dresden, Germany, at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition. “This is the first randomized trial evidence for clinical benefit for a tyrosine kinase inhibitor in previously untreated acute myeloid leukemia. A confirmatory trial is needed to establish this as a new standard for acute myeloid leukemia,” he added.

The addition of sorafenib was associated with more frequent toxicities, including fever, diarrhea, bleeding events, liver toxicity, hand-foot syndrome, and rash.

Prior to the SORAML trial, evidence from case reports and early-phase, nonrandomized trials suggested a benefit for sorafenib in acute myeloid leukemia. Hubert Serve, MD, and colleagues from Dr. Röllig’s German SAL study group conducted a trial comparing sorafenib vs placebo in addition to chemotherapy in the first-line setting in elderly patients and found no benefit.2

SORAML was designed to study sorafenib in younger patients with acute myeloid leukemia. Following the diagnosis of acute myeloid leukemia, 267 patients (aged 18 to 60 years) were randomly assigned to receive two cycles of induction chemotherapy (daunorubicin and cytarabine) plus sorafenib vs placebo. Patients with intermediate or high cytogenetic risk who achieved remission on induction and had suitable donors went on to transplant; the others went on to three cycles of consolidation with high-dose chemotherapy plus or minus sorafenib followed by 1 year of maintenance with sorafenib vs placebo. Sorafenib was not given concomitantly with chemotherapy.

The median age of the study patients was 50 years. About 87% had de novo acute myeloid leukemia, and about 17% had FLT3-ITD–positive disease; about one-third had NPM1 mutations.

Study Results

The complete response rate was similar between the groups: 60% in the sorafenib group vs 59% in the placebo group.

Event-free survival, the primary endpoint, was significantly prolonged in the sorafenib arm. At a median follow-up of 36 months, the median event-free survival was 21 months for sorafenib vs 9 months for placebo (P = .013).

A similar pattern was observed for relapse-free survival at 3 years: 56% vs 38%, respectively. The median relapse-free survival has not yet been reached for sorafenib and was 23 months for placebo.

Three-year overall survival was 63% for sorafenib vs 56% for placebo. The median overall survival for sorafenib vs placebo has not yet been reached.

In the 46 patients who had FLT3-ITD–positive disease, no difference between the treatment arms was observed for event-free survival, but relapse-free survival and overall survival trended in favor of sorafenib. ■

Disclosure:  Bayer Healthcare Germany provided research funding for this study.


1. Röllig C, et al: Sorafenib versus placebo in addition to standard therapy in younger patients with newly diagnosed acute myeloid leukemia. 2014 ASH Annual Meeting. Abstract 6. Presented December 7, 2014.

2. Serve H, et al: Sorafenib in combination with intensive chemotherapy in elderly patients with acute myeloid leukemia. J Clin Oncol 31:3110-3118, 2013.

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