title: International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts.
abstract: This multicenter, randomized, open-label, phase 3 trial evaluated azacitidine efficacy and safety vs conventional care regimens (CCRs) in 488 patients age ≥65 years with newly diagnosed acute myeloid leukemia (AML) with >30% bone marrow blasts. Before randomization, a CCR (standard induction chemotherapy, low-dose ara-c, or supportive care only) was preselected for each patient. Patients then were assigned 1:1 to azacitidine (n = 241) or CCR (n = 247). Patients assigned to CCR received their preselected treatment. Median overall survival (OS) was increased with azacitidine vs CCR: 10.4 months (95% confidence interval [CI], 8.0-12.7 months) vs 6.5 months (95% CI, 5.0-8.6 months), respectively (hazard ratio [HR] was 0.85; 95% CI, 0.69-1.03; stratified log-rank P = .1009). One-year survival rates with azacitidine and CCR were 46.5% and 34.2%, respectively (difference, 12.3%; 95% CI, 3.5%-21.0%). A prespecified analysis censoring patients who received AML treatment after discontinuing study drug showed median OS with azacitidine vs CCR was 12.1 months (95% CI, 9.2-14.2 months) vs 6.9 months (95% CI, 5.1-9.6 months; HR, 0.76; 95% CI, 0.60-0.96; stratified log-rank P = .0190). Univariate analysis showed favorable trends for azacitidine compared with CCR across all subgroups defined by baseline demographic and disease features. Adverse events were consistent with the well-established safety profile of azacitidine. Azacitidine may be an important treatment option for this difficult-to-treat AML population. This trial was registered at www.clinicaltrials.gov as #NCT01074047.
authors.affiliation: Hôpital Saint Louis, Institut Universitaire d'Hématologie, University Paris Diderot, Paris, France;
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
authors.affiliation: Peter MacCallum Cancer Centre, East Melbourne, Australia, and University of Melbourne, Parkville, Australia;
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.affiliation: Wroclaw Medical University, Wroclaw, Poland;
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Butrym
authors.affiliation: Medical University of Lodz, Lodz, Poland;
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wierzbowska
authors.affiliation: Algemeen Ziekenhuis Sint-Jan, Brugge, Belgium;
authors.forename: Dominik
authors.initials: D
authors.lastname: Selleslag
authors.affiliation: Samsung Medical Center, Seoul, Republic of Korea;
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Cancer Care Manitoba, Winnipeg, Canada;
authors.forename: Rajat
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Barts Health National Health Service Trust, London, United Kingdom;
authors.forename: James
authors.initials: J
authors.lastname: Cavenagh
authors.affiliation: Princess Margaret Cancer Centre, Toronto, Canada;
authors.forename: Andre C
authors.initials: AC
authors.lastname: Schuh
authors.affiliation: Azienda Ospedaliero Universitaria S. Maria della Misericordia di Udine, Udine, Italy;
authors.forename: Anna
authors.initials: A
authors.lastname: Candoni
authors.affiliation: Centre Hospitalier Universitaire de Toulouse, Toulouse, France;
authors.forename: Christian
authors.initials: C
authors.lastname: Récher
authors.affiliation: University of Alberta Hospital, Edmonton, Canada;
authors.forename: Irwindeep
authors.initials: I
authors.lastname: Sandhu
authors.affiliation: Hospital Central de Asturias, Oviedo, Spain;
authors.forename: Teresa
authors.initials: T
authors.lastname: Bernal del Castillo
authors.affiliation: Universitätsklinikum Leipzig, Leipzig, Germany;
authors.forename: Haifa Kathrin
authors.initials: HK
authors.lastname: Al-Ali
authors.affiliation: Institute of Hematology and Medical Oncology "L. e A. Seràgnoli," Bologna, Italy;
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.affiliation: Hospital Universitario Virgen del Rocio/Instituto de BioMedicinia de Sevilla, Sevilla, Spain;
authors.forename: Jose
authors.initials: J
authors.lastname: Falantes
authors.affiliation: Universitätsklinikum Essen Klinik für Hämatologie, Essen, Germany;
authors.forename: Richard
authors.initials: R
authors.lastname: Noppeney
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.affiliation: Princess Margaret Cancer Centre, Toronto, Canada;
authors.forename: Mark D
authors.initials: MD
authors.lastname: Minden
authors.affiliation: Celgene Corporation, Summit, NJ; and.
authors.forename: Heidi
authors.initials: H
authors.lastname: McIntyre
authors.affiliation: Celgene Corporation, Summit, NJ; and.
authors.forename: Steve
authors.initials: S
authors.lastname: Songer
authors.affiliation: Celgene Corporation, Summit, NJ; and.
authors.forename: Lela M
authors.initials: LM
authors.lastname: Lucy
authors.affiliation: Celgene Corporation, Summit, NJ; and.
authors.forename: C L
authors.initials: CL
authors.lastname: Beach
authors.affiliation: Universitätsklinikum Ulm, Ulm, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use*; D001752:Blast Crisis / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007390:International Agencies; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine