The European Medicines Agency Review of Decitabine (Dacogen) for the Treatment of Adult Patients With Acute Myeloid Leukemia: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use.
: On September 20, 2012, a marketing authorization valid throughout the European Union (EU) was issued for decitabine for the treatment of adult patients aged 65 years and older with newly diagnosed de novo or secondary acute myeloid leukemia (AML) who are not candidates for standard induction chemotherapy. Decitabine is a pyrimidine analog incorporated into DNA, where it irreversibly inhibits DNA methyltransferases through covalent adduct formation with the enzyme. The use of decitabine was studied in an open-label, randomized, multicenter phase III study (DACO-016) in patients with newly diagnosed de novo or secondary AML. Decitabine (n = 242) was compared with patient's choice with physician's advice (n = 243) of low-dose cytarabine or supportive care alone. The primary endpoint of the study was overall survival. The median overall survival in the intent-to-treat (ITT) population was 7.7 months among patients treated with decitabine compared with 5.0 months for those in the control arm (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.69-1.04; p = .1079). Mature survival data after an additional year of follow-up were consistent with these results, with a median overall survival of 7.7 months in patients treated with decitabine and 5.0 months in the control arm (HR, 0.82; 95% CI, 0.68-0.99; p = .0373). Secondary endpoints, including response rates, progression-free survival, and event-free survival, were increased in favor of decitabine when compared with control treatment. The most common adverse drug reactions reported during treatment with decitabine are pyrexia, anemia, thrombocytopenia, febrile neutropenia, neutropenia, nausea, and diarrhea. This paper summarizes the scientific review of the application leading to approval of decitabine in the EU. The detailed scientific assessment report and product information (including the summary of product characteristics) for this product are available on the EMA website (http://www.ema.europa.eu).



Acute myeloid leukemia (AML) remains an area of significant unmet need, especially in older patients. Older patients and those with comorbidities are often considered ineligible for standard induction therapy, and outcome for these patients is poor. Decitabine has favorable effects in terms of overall survival, which were considered clinically meaningful in the context of a manageable toxicity profile and after consideration of the lack of therapeutic alternatives for these patients. Decitabine is widely used in the treatment of AML in patients aged >60 years, as per current guidelines, including the European LeukemiaNet and the U.S. National Cancer Comprehensive Network.
European Medicines Agency, London, United Kingdom Maria.NietoGutierrez@ema.europa.eu.
Maria
M
Nieto
French National Agency for Medicines and Health Products Safety, Saint-Denis Cedex, France.
Pierre
P
Demolis
French National Agency for Medicines and Health Products Safety, Saint-Denis Cedex, France.
Eliane
E
Béhanzin
French National Agency for Medicines and Health Products Safety, Saint-Denis Cedex, France.
Alexandre
A
Moreau
Medicines and Healthcare Products Regulatory Agency, London, United Kingdom.
Ian
I
Hudson
Medicines and Healthcare Products Regulatory Agency, London, United Kingdom.
Beatriz
B
Flores
Medicines and Healthcare Products Regulatory Agency, London, United Kingdom.
Henry
H
Stemplewski
Läkemedelsverket, Medical Products Agency, Uppsala, Sweden.
Tomas
T
Salmonson
Hospital Saint Louis, Paris, France.
Christian
C
Gisselbrecht
European Medicines Agency, London, United Kingdom.
David
D
Bowen
European Medicines Agency, London, United Kingdom.
Francesco
F
Pignatti
D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077209:Decitabine; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male
D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine
Acute myeloid leukemia; Dacogen; Decitabine; European Medicines Agency