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Phase III Study of Dacogen (decitabine) for Injection in Acute Myeloid Leukemia (AML) Presented at ASCO

CHICAGO--(BUSINESS WIRE)--Jun 6, 2011 - Results from the DACO-016 trial of Dacogen® (decitabine) in acute myeloid leukemia (AML) were presented today at the 2011 Annual Meeting of the American Society of Clinical Oncology (ASCO). AML is a life-threatening cancer of the blood for which there are limited treatment options.

The 485-patient, open-label, multi-center study compared Dacogen versus treatment choice (TC) of either supportive care or low-dose cytarabine in older patients with newly diagnosed or secondary AML. The primary endpoint of the study was overall survival.

The results of the analysis showed that at the protocol-defined clinical cutoff, with 396 (81.6%) deaths, Dacogen demonstrated an overall survival advantage but did not demonstrate statistically significant superiority over the control arm. Patients treated with Dacogen had a median survival of 7.7 months (HR 0.85: 95% CI: 6.2, 9.2, p=0.108) versus 5.0 months (95% CI: 4.3, 6.3) in the TC arm.

The updated unplanned analysis, conducted with an additional year of patient follow-up, demonstrated the same median survival benefit for patients treated with Dacogen. With 446 (92%) deaths, it showed that patients in the Dacogen arm had a median survival of 7.7 months vs. 5 months in the TC arm (HR 0.82: 95% CI: 0.68, 0.99: nominal p=0.037).

Adverse events were consistent with the known Dacogen safety profile and without major differences between the treatment arms. The most commonly reported Grade 3 or 4 adverse events were thrombocytopenia (reported in 40%, 32%, 35% and 14% of subjects in the Dacogen, TC, cytarabine and supportive care groups, respectively), anemia (34%, 25%, 27% and 14%, respectively), neutropenia (32%, 42%, 20% and 3%, respectively) and febrile neutropenia (32%, 22%, 25% and 0%, respectively).

“Compared with the accepted standard therapies used in this study to treat older patients with AML, Dacogen showed a clinically relevant overall survival advantage without major differences in safety,” said Dr. Xavier Thomas of the Edouard Herriot Hospital in Lyon, France and one of the lead investigators of the study.

About the Study

DACO-016 was a Phase III randomized open-label, multi-center trial comparing DACOGEN versus patient's choice with physician's advice of either supportive care or low-dose cytarabine in patients 65 years and older with newly diagnosed de novo or secondary acute myeloid leukemia (AML) and with poor- or intermediate-risk cytogenetics.

Of the 485 patients, 242 were randomized to Dacogen and 243 to patient's treatment choice of supportive care or low-dose cytarabine. Dacogen was administered at 20 mg/m² for one hour by intravenous infusion once daily for five consecutive days repeated every four weeks, continued as long as the patient derived benefit. Patients treated with cytarabine received 20mg/m² subcutaneously once daily 10 consecutive days every 4 weeks. The median duration of treatment for patients on Dacogen was 4.4 months, compared with 2.4 months in the cytarabine group.

DACO-016 is the largest randomized controlled study in older patients with AML.

About Dacogen

Dacogen is approved for treatment of patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS of all French-American-British (FAB) subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia), and Intermediate-1, Intermediate-2 and High-Risk International Prognostic Scoring System (IPSS) groups.

Important Safety Information

Treatment with DACOGEN is associated with neutropenia and thrombocytopenia. Complete blood and platelet counts should be performed as needed to monitor response and toxicity but at a minimum prior to each dosing cycle. After administration of the recommended dosage for the first cycle, treatment for subsequent cycles should be adjusted if indicated by dose adjustment guidelines. Clinicians should consider the need for early institution of growth factors and/or antimicrobial agents for the prevention or treatment of infections in patients with MDS.

DACOGEN may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with DACOGEN and for 1 month following completion of treatment. Women of childbearing potential should be counseled to use effective contraception during this time. Men should be advised not to father a child while receiving treatment with DACOGEN and for 2 months following completion of treatment. DACOGEN may cause fetal harm. Men with female partners of childbearing potential should use effective contraception during this time.

In the phase 3 clinical trial, the highest incidence of Grade 3 or Grade 4 adverse events in the DACOGEN arm was neutropenia (87%), thrombocytopenia (85%), febrile neutropenia (23%), and leukopenia (22%). Bone marrow suppression was the most frequent cause of dose reduction, delay, and discontinuation. Six patients had fatal events associated with their underlying disease and myelosuppression (anemia, neutropenia, and thrombocytopenia) that were considered at least possibly related to drug treatment. Of the 83 DACOGEN-treated patients, 8 permanently discontinued therapy for adverse events compared to 1 of 81 patients in the supportive care arm.

In the single-arm study, the highest incidence of Grade 3 or Grade 4 adverse events was neutropenia (37%), thrombocytopenia (24%), and anemia (22%). Seventy-eight percent of patients had dose delays, the median duration of this delay was 7 days. Hematologic toxicities and infections were the most frequent causes of dose delays and discontinuation. Eight patients had fatal events due to infection and/or bleeding that were considered at least possibly related to drug treatment. Nineteen of 99 patients permanently discontinued therapy for adverse events.

Other commonly occurring reactions include fatigue, pyrexia, nausea, cough, petechiae, constipation, diarrhea, and hyperglycemia.

If hematologic recovery from a previous DACOGEN treatment cycle requires more than 6 weeks when administering the 3-day dosing, then the next DACOGEN cycle should be delayed and dosing temporarily reduced. When administering the 5-day dosing, the DACOGEN cycle should be delayed until there is hematologic recovery. If the following nonhematologic toxicities are present, DACOGEN treatment should not be restarted until the toxicity is resolved: (1) serum creatinine ‰¥2 mg/dL; (2) SGPt, total bilirubin ‰¥2 × ULN; and (3) active or uncontrolled infection.

Because there are no data on use of DACOGEN in patients with renal or hepatic dysfunction, DACOGEN should be used with caution in these patients.

For DACOGEN full prescribing information, please click here.

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Contact: Eisai Inc.
Media Inquiries
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During ASCO: 973-493-7971
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Posted: June 2011