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Credit: NIH
In a phase 2 study, the anticancer quinolone derivative vosaroxin produced responses in poor-risk, elderly patients with previously untreated acute myeloid leukemia (AML), but most patients ultimately died.
Twenty-nine percent of patients achieved a complete response (CR) following treatment with vosaroxin.
However, 84% of patients discontinued treatment, most due to treatment failure. And 91% of patients died, most from disease progression.
Still, study investigators said single-agent vosaroxin shows promise as a treatment option for this group of patients, who are unlikely to benefit from standard induction chemotherapy.
“There remains an acute unmet medical need for new treatment options in AML, including patients 60 years of age and older who are unlikely to benefit from standard induction chemotherapy,” said Farhad Ravandi, MD, of the University of Texas MD Anderson Cancer Center.
“Vosaroxin is active and well-tolerated in this population, both as a single agent, as seen in [this] study, and in combination with decitabine, as seen in an ongoing MD Anderson Cancer Center-sponsored study.”
Dr Ravandi and his colleagues reported results of the phase 2 trial, called REVEAL-1, in the British Journal of Haematology. The study was sponsored by Sunesis Pharmaceuticals, the company developing vosaroxin.
The investigators evaluated vosaroxin in 113 patients aged 60 and older who had previously untreated AML with an unfavorable prognosis.
The patients’ median age was 75 years, and most (82%) had 2 or more risk factors, which included being 70 or older, having antecedent hematologic disease, having an ECOG performance status of 2, and having intermediate/unfavorable cytogenetics.
Patients received vosaroxin in sequential cohorts. In group A, they received 72 mg/m2 on days 1, 8, and 15. In group B, they received 72 mg/m2 on days 1 and 8. And in group C, they received 72 mg/m2 or 90 mg/m2 on days 1 and 4.
The primary efficacy endpoint was the combined CR rate and the rate of CR with incomplete platelet recovery (CRp). CR and CR/CRp rates were 29% and 32%, respectively. Responses occurred in all categories of risk factors, including in patients with 2 or more risk factors.
Ninety-five patients (84%) discontinued treatment due to treatment failure (n=50), death (n=21), unacceptable adverse events (n=6), relapse (n=5), their physician’s decision (n=5) or other reasons (n=8).
The all-cause mortality rate was 12% at 30 days and 31% at 60 days. The median overall survival (OS) was 7.0 months, and the 1-year OS rate was 34%.
Common grade 3/4 hematologic adverse events (occurring in 20% of patients or more) included thrombocytopenia (59%), febrile neutropenia (50%), anemia (49%), and neutropenia (29%).
Common grade 3/4 nonhematologic adverse events included sepsis (39%), pneumonia (30%), hypokalemia (25%), and oral mucositis/stomatitis (22%).
Ninety-one patients (81%) had one or more serious adverse event. The most common were pneumonia (24%), febrile neutropenia (21%), and oral mucositis/stomatitis (10%).
Of the 113 patients treated, 103 died. Most deaths (78%) were due to progressive disease.
Patients in group C (72 mg/m2) had the most favorable balance of safety and efficacy. They had faster hematologic recovery (a median of 27 days) than the other groups and the lowest incidence of aggregate sepsis (24%) and 30-day (7%) and 60-day (17%) all-cause mortality.
At this dose and schedule, CR and CR/CRp rates were 31% and 35%, respectively. The median OS was 7.7 months, and the 1-year OS rate was 38%.
“Publication of these data in the British Journal of Haematology further support our goal of establishing vosaroxin as a new standard of care in AML,” said Adam Craig, chief medical officer of Sunesis.
“Given ongoing demographic shifts in the US and other major territories, the challenge of treating AML in older adults will continue to grow, underscoring a need for new treatment options. We look forward to building on these data through further investigator-sponsored studies and, with the outcome of VALOR in relapsed or refractory AML, progressing towards initial regulatory approval.”
Based on results of the phase 3 VALOR trial, which were recently announced, Sunesis has filed a marketing authorization application with the European Medicines Agency and plans to meet with the US Food and Drug Administration to determine the appropriate regulatory path forward for vosaroxin in the treatment of relapsed or refractory AML. 
Credit: NIH
In a phase 2 study, the anticancer quinolone derivative vosaroxin produced responses in poor-risk, elderly patients with previously untreated acute myeloid leukemia (AML), but most patients ultimately died.
Twenty-nine percent of patients achieved a complete response (CR) following treatment with vosaroxin.
However, 84% of patients discontinued treatment, most due to treatment failure. And 91% of patients died, most from disease progression.
Still, study investigators said single-agent vosaroxin shows promise as a treatment option for this group of patients, who are unlikely to benefit from standard induction chemotherapy.
“There remains an acute unmet medical need for new treatment options in AML, including patients 60 years of age and older who are unlikely to benefit from standard induction chemotherapy,” said Farhad Ravandi, MD, of the University of Texas MD Anderson Cancer Center.
“Vosaroxin is active and well-tolerated in this population, both as a single agent, as seen in [this] study, and in combination with decitabine, as seen in an ongoing MD Anderson Cancer Center-sponsored study.”
Dr Ravandi and his colleagues reported results of the phase 2 trial, called REVEAL-1, in the British Journal of Haematology. The study was sponsored by Sunesis Pharmaceuticals, the company developing vosaroxin.
The investigators evaluated vosaroxin in 113 patients aged 60 and older who had previously untreated AML with an unfavorable prognosis.
The patients’ median age was 75 years, and most (82%) had 2 or more risk factors, which included being 70 or older, having antecedent hematologic disease, having an ECOG performance status of 2, and having intermediate/unfavorable cytogenetics.
Patients received vosaroxin in sequential cohorts. In group A, they received 72 mg/m2 on days 1, 8, and 15. In group B, they received 72 mg/m2 on days 1 and 8. And in group C, they received 72 mg/m2 or 90 mg/m2 on days 1 and 4.
The primary efficacy endpoint was the combined CR rate and the rate of CR with incomplete platelet recovery (CRp). CR and CR/CRp rates were 29% and 32%, respectively. Responses occurred in all categories of risk factors, including in patients with 2 or more risk factors.
Ninety-five patients (84%) discontinued treatment due to treatment failure (n=50), death (n=21), unacceptable adverse events (n=6), relapse (n=5), their physician’s decision (n=5) or other reasons (n=8).
The all-cause mortality rate was 12% at 30 days and 31% at 60 days. The median overall survival (OS) was 7.0 months, and the 1-year OS rate was 34%.
Common grade 3/4 hematologic adverse events (occurring in 20% of patients or more) included thrombocytopenia (59%), febrile neutropenia (50%), anemia (49%), and neutropenia (29%).
Common grade 3/4 nonhematologic adverse events included sepsis (39%), pneumonia (30%), hypokalemia (25%), and oral mucositis/stomatitis (22%).
Ninety-one patients (81%) had one or more serious adverse event. The most common were pneumonia (24%), febrile neutropenia (21%), and oral mucositis/stomatitis (10%).
Of the 113 patients treated, 103 died. Most deaths (78%) were due to progressive disease.
Patients in group C (72 mg/m2) had the most favorable balance of safety and efficacy. They had faster hematologic recovery (a median of 27 days) than the other groups and the lowest incidence of aggregate sepsis (24%) and 30-day (7%) and 60-day (17%) all-cause mortality.
At this dose and schedule, CR and CR/CRp rates were 31% and 35%, respectively. The median OS was 7.7 months, and the 1-year OS rate was 38%.
“Publication of these data in the British Journal of Haematology further support our goal of establishing vosaroxin as a new standard of care in AML,” said Adam Craig, chief medical officer of Sunesis.
“Given ongoing demographic shifts in the US and other major territories, the challenge of treating AML in older adults will continue to grow, underscoring a need for new treatment options. We look forward to building on these data through further investigator-sponsored studies and, with the outcome of VALOR in relapsed or refractory AML, progressing towards initial regulatory approval.”
Based on results of the phase 3 VALOR trial, which were recently announced, Sunesis has filed a marketing authorization application with the European Medicines Agency and plans to meet with the US Food and Drug Administration to determine the appropriate regulatory path forward for vosaroxin in the treatment of relapsed or refractory AML.
Credit: NIH
In a phase 2 study, the anticancer quinolone derivative vosaroxin produced responses in poor-risk, elderly patients with previously untreated acute myeloid leukemia (AML), but most patients ultimately died.
Twenty-nine percent of patients achieved a complete response (CR) following treatment with vosaroxin.
However, 84% of patients discontinued treatment, most due to treatment failure. And 91% of patients died, most from disease progression.
Still, study investigators said single-agent vosaroxin shows promise as a treatment option for this group of patients, who are unlikely to benefit from standard induction chemotherapy.
“There remains an acute unmet medical need for new treatment options in AML, including patients 60 years of age and older who are unlikely to benefit from standard induction chemotherapy,” said Farhad Ravandi, MD, of the University of Texas MD Anderson Cancer Center.
“Vosaroxin is active and well-tolerated in this population, both as a single agent, as seen in [this] study, and in combination with decitabine, as seen in an ongoing MD Anderson Cancer Center-sponsored study.”
Dr Ravandi and his colleagues reported results of the phase 2 trial, called REVEAL-1, in the British Journal of Haematology. The study was sponsored by Sunesis Pharmaceuticals, the company developing vosaroxin.
The investigators evaluated vosaroxin in 113 patients aged 60 and older who had previously untreated AML with an unfavorable prognosis.
The patients’ median age was 75 years, and most (82%) had 2 or more risk factors, which included being 70 or older, having antecedent hematologic disease, having an ECOG performance status of 2, and having intermediate/unfavorable cytogenetics.
Patients received vosaroxin in sequential cohorts. In group A, they received 72 mg/m2 on days 1, 8, and 15. In group B, they received 72 mg/m2 on days 1 and 8. And in group C, they received 72 mg/m2 or 90 mg/m2 on days 1 and 4.
The primary efficacy endpoint was the combined CR rate and the rate of CR with incomplete platelet recovery (CRp). CR and CR/CRp rates were 29% and 32%, respectively. Responses occurred in all categories of risk factors, including in patients with 2 or more risk factors.
Ninety-five patients (84%) discontinued treatment due to treatment failure (n=50), death (n=21), unacceptable adverse events (n=6), relapse (n=5), their physician’s decision (n=5) or other reasons (n=8).
The all-cause mortality rate was 12% at 30 days and 31% at 60 days. The median overall survival (OS) was 7.0 months, and the 1-year OS rate was 34%.
Common grade 3/4 hematologic adverse events (occurring in 20% of patients or more) included thrombocytopenia (59%), febrile neutropenia (50%), anemia (49%), and neutropenia (29%).
Common grade 3/4 nonhematologic adverse events included sepsis (39%), pneumonia (30%), hypokalemia (25%), and oral mucositis/stomatitis (22%).
Ninety-one patients (81%) had one or more serious adverse event. The most common were pneumonia (24%), febrile neutropenia (21%), and oral mucositis/stomatitis (10%).
Of the 113 patients treated, 103 died. Most deaths (78%) were due to progressive disease.
Patients in group C (72 mg/m2) had the most favorable balance of safety and efficacy. They had faster hematologic recovery (a median of 27 days) than the other groups and the lowest incidence of aggregate sepsis (24%) and 30-day (7%) and 60-day (17%) all-cause mortality.
At this dose and schedule, CR and CR/CRp rates were 31% and 35%, respectively. The median OS was 7.7 months, and the 1-year OS rate was 38%.
“Publication of these data in the British Journal of Haematology further support our goal of establishing vosaroxin as a new standard of care in AML,” said Adam Craig, chief medical officer of Sunesis.
“Given ongoing demographic shifts in the US and other major territories, the challenge of treating AML in older adults will continue to grow, underscoring a need for new treatment options. We look forward to building on these data through further investigator-sponsored studies and, with the outcome of VALOR in relapsed or refractory AML, progressing towards initial regulatory approval.”
Based on results of the phase 3 VALOR trial, which were recently announced, Sunesis has filed a marketing authorization application with the European Medicines Agency and plans to meet with the US Food and Drug Administration to determine the appropriate regulatory path forward for vosaroxin in the treatment of relapsed or refractory AML.