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Photo courtesy of ASH
SAN FRANCISCO—Researchers have presented the first randomized evidence that kinase inhibitors are effective in the treatment of acute myeloid leukemia
(AML).
The multikinase inhibitor sorafenib improved event-free and relapse-free survival in younger patients.
“Interestingly, at this point in time, we can see no clear overall survival benefit for patients treated in the sorafenib arm,” said trial investigator Christoph Röllig, MD, of the Universitätsklinikum Dresden in Germany.
Dr Röllig, representing the Study Alliance Leukemia, presented data on sorafenib from the SORAML trial during the plenary session of the 2014 ASH Annual Meeting (abstract 6). Some funding for this trial was provided by Bayer Healthcare, the company developing sorafenib.
Dr Röllig explained that support for sorafenib’s clinical efficacy in AML was based primarily on case series and a few early phase clinical and nonrandomized
trials.
An earlier randomized study with sorafenib in older AML patients showed no beneficial antileukemic effect with the addition of the agent, and the treatment was associated with significant morbidity.
However, because the biology of AML and drug tolerance are different in younger people, the Study Alliance Leukemia decided to test the drug in a younger
patient population.
They randomized 276 newly diagnosed AML patients aged 60 years or younger to receive 2 cycles of induction chemotherapy with an anthracycline and cytarabine plus either sorafenib or placebo.
The sorafenib dose was 800 mg per day orally. All patients received at least one dose of study medication, forming the statistical analysis set.
Once in complete remission, intermediate-risk patients with a family donor and high-risk patients with a matched donor went on to stem cell transplant.
All other patients proceeded to high-dose cytarabine-based consolidation treatment plus sorafenib or placebo followed by 1 year of maintenance treatment with sorafenib or placebo.
The primary endpoint was event-free survival (EFS). An event was defined as primary treatment failure, relapse, or death.
Patients in each arm were a median age of 50 years, 17% were FLT3-ITD positive, and 33% were NPM1 mutated.
The complete response (CR) rate was 60% in the sorafenib arm and 59% in the placebo arm. Patients with FLT3-ITD mutation achieved a 57% CR rate with sorafenib and a 52% CR rate with placebo.
After a median follow-up of 3 years, investigators observed “significant prolongation of event-free survival in the sorafenib arm,” Dr Röllig said.
Patients on the sorafenib arm had a median EFS of 40% compared with 22% on the placebo arm, or 21 months compared with 9 months (P=0.013).
Patients were censored at the time of transplant. However, uncensored results were very similar, Dr Röllig noted, “with an even greater advantage for sorafenib.”
Fifty-six percent of sorafenib-treated patients were relapse-free and alive after 3 years, compared with 38% of patients on placebo (P=0.017).
The 3-year overall survival was 63% in the sorafenib arm and 56% in the placebo arm (P=0.382).
An exploratory analysis of FLT3-ITD patients revealed that 1-year EFS for sorafenib-treated patients was 54%, and, for placebo-treated patients, it was 50%.
“The reasons for potential efficacy of sorafenib in this mainly FLT3-ITD-negative population must remain speculative,” Dr Röllig said. “We can speculate that the inhibition of other kinases apart from FLT3 might be responsible for the efficacy of this drug in this patient population.”
Sorafenib significantly increased the risk of grade 3 or greater hand-foot syndrome (P<0.001), diarrhea (P=0.001), bleeding (P=0.016), rash (P=0.045), liver toxicity (P=0.048), and fever (P=0.035).
Dr Röllig indicated a confirmatory trial would be desirable in order to establish sorafenib in the AML treatment armamentarium. 
Photo courtesy of ASH
SAN FRANCISCO—Researchers have presented the first randomized evidence that kinase inhibitors are effective in the treatment of acute myeloid leukemia
(AML).
The multikinase inhibitor sorafenib improved event-free and relapse-free survival in younger patients.
“Interestingly, at this point in time, we can see no clear overall survival benefit for patients treated in the sorafenib arm,” said trial investigator Christoph Röllig, MD, of the Universitätsklinikum Dresden in Germany.
Dr Röllig, representing the Study Alliance Leukemia, presented data on sorafenib from the SORAML trial during the plenary session of the 2014 ASH Annual Meeting (abstract 6). Some funding for this trial was provided by Bayer Healthcare, the company developing sorafenib.
Dr Röllig explained that support for sorafenib’s clinical efficacy in AML was based primarily on case series and a few early phase clinical and nonrandomized
trials.
An earlier randomized study with sorafenib in older AML patients showed no beneficial antileukemic effect with the addition of the agent, and the treatment was associated with significant morbidity.
However, because the biology of AML and drug tolerance are different in younger people, the Study Alliance Leukemia decided to test the drug in a younger
patient population.
They randomized 276 newly diagnosed AML patients aged 60 years or younger to receive 2 cycles of induction chemotherapy with an anthracycline and cytarabine plus either sorafenib or placebo.
The sorafenib dose was 800 mg per day orally. All patients received at least one dose of study medication, forming the statistical analysis set.
Once in complete remission, intermediate-risk patients with a family donor and high-risk patients with a matched donor went on to stem cell transplant.
All other patients proceeded to high-dose cytarabine-based consolidation treatment plus sorafenib or placebo followed by 1 year of maintenance treatment with sorafenib or placebo.
The primary endpoint was event-free survival (EFS). An event was defined as primary treatment failure, relapse, or death.
Patients in each arm were a median age of 50 years, 17% were FLT3-ITD positive, and 33% were NPM1 mutated.
The complete response (CR) rate was 60% in the sorafenib arm and 59% in the placebo arm. Patients with FLT3-ITD mutation achieved a 57% CR rate with sorafenib and a 52% CR rate with placebo.
After a median follow-up of 3 years, investigators observed “significant prolongation of event-free survival in the sorafenib arm,” Dr Röllig said.
Patients on the sorafenib arm had a median EFS of 40% compared with 22% on the placebo arm, or 21 months compared with 9 months (P=0.013).
Patients were censored at the time of transplant. However, uncensored results were very similar, Dr Röllig noted, “with an even greater advantage for sorafenib.”
Fifty-six percent of sorafenib-treated patients were relapse-free and alive after 3 years, compared with 38% of patients on placebo (P=0.017).
The 3-year overall survival was 63% in the sorafenib arm and 56% in the placebo arm (P=0.382).
An exploratory analysis of FLT3-ITD patients revealed that 1-year EFS for sorafenib-treated patients was 54%, and, for placebo-treated patients, it was 50%.
“The reasons for potential efficacy of sorafenib in this mainly FLT3-ITD-negative population must remain speculative,” Dr Röllig said. “We can speculate that the inhibition of other kinases apart from FLT3 might be responsible for the efficacy of this drug in this patient population.”
Sorafenib significantly increased the risk of grade 3 or greater hand-foot syndrome (P<0.001), diarrhea (P=0.001), bleeding (P=0.016), rash (P=0.045), liver toxicity (P=0.048), and fever (P=0.035).
Dr Röllig indicated a confirmatory trial would be desirable in order to establish sorafenib in the AML treatment armamentarium.
Photo courtesy of ASH
SAN FRANCISCO—Researchers have presented the first randomized evidence that kinase inhibitors are effective in the treatment of acute myeloid leukemia
(AML).
The multikinase inhibitor sorafenib improved event-free and relapse-free survival in younger patients.
“Interestingly, at this point in time, we can see no clear overall survival benefit for patients treated in the sorafenib arm,” said trial investigator Christoph Röllig, MD, of the Universitätsklinikum Dresden in Germany.
Dr Röllig, representing the Study Alliance Leukemia, presented data on sorafenib from the SORAML trial during the plenary session of the 2014 ASH Annual Meeting (abstract 6). Some funding for this trial was provided by Bayer Healthcare, the company developing sorafenib.
Dr Röllig explained that support for sorafenib’s clinical efficacy in AML was based primarily on case series and a few early phase clinical and nonrandomized
trials.
An earlier randomized study with sorafenib in older AML patients showed no beneficial antileukemic effect with the addition of the agent, and the treatment was associated with significant morbidity.
However, because the biology of AML and drug tolerance are different in younger people, the Study Alliance Leukemia decided to test the drug in a younger
patient population.
They randomized 276 newly diagnosed AML patients aged 60 years or younger to receive 2 cycles of induction chemotherapy with an anthracycline and cytarabine plus either sorafenib or placebo.
The sorafenib dose was 800 mg per day orally. All patients received at least one dose of study medication, forming the statistical analysis set.
Once in complete remission, intermediate-risk patients with a family donor and high-risk patients with a matched donor went on to stem cell transplant.
All other patients proceeded to high-dose cytarabine-based consolidation treatment plus sorafenib or placebo followed by 1 year of maintenance treatment with sorafenib or placebo.
The primary endpoint was event-free survival (EFS). An event was defined as primary treatment failure, relapse, or death.
Patients in each arm were a median age of 50 years, 17% were FLT3-ITD positive, and 33% were NPM1 mutated.
The complete response (CR) rate was 60% in the sorafenib arm and 59% in the placebo arm. Patients with FLT3-ITD mutation achieved a 57% CR rate with sorafenib and a 52% CR rate with placebo.
After a median follow-up of 3 years, investigators observed “significant prolongation of event-free survival in the sorafenib arm,” Dr Röllig said.
Patients on the sorafenib arm had a median EFS of 40% compared with 22% on the placebo arm, or 21 months compared with 9 months (P=0.013).
Patients were censored at the time of transplant. However, uncensored results were very similar, Dr Röllig noted, “with an even greater advantage for sorafenib.”
Fifty-six percent of sorafenib-treated patients were relapse-free and alive after 3 years, compared with 38% of patients on placebo (P=0.017).
The 3-year overall survival was 63% in the sorafenib arm and 56% in the placebo arm (P=0.382).
An exploratory analysis of FLT3-ITD patients revealed that 1-year EFS for sorafenib-treated patients was 54%, and, for placebo-treated patients, it was 50%.
“The reasons for potential efficacy of sorafenib in this mainly FLT3-ITD-negative population must remain speculative,” Dr Röllig said. “We can speculate that the inhibition of other kinases apart from FLT3 might be responsible for the efficacy of this drug in this patient population.”
Sorafenib significantly increased the risk of grade 3 or greater hand-foot syndrome (P<0.001), diarrhea (P=0.001), bleeding (P=0.016), rash (P=0.045), liver toxicity (P=0.048), and fever (P=0.035).
Dr Röllig indicated a confirmatory trial would be desirable in order to establish sorafenib in the AML treatment armamentarium.