Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial

Autor: Stéphane de Botton, Pau Montesinos, Andre C. Schuh, Cristina Papayannidis, Paresh Vyas, Andrew H. Wei, Hans Ommen, Sergey Semochkin, Hee-Je Kim, Richard A. Larson, Jaime Koprivnikar, Olga Frankfurt, Felicitas Thol, Jörg Chromik, Jenny Byrne, Arnaud Pigneux, Xavier Thomas, Olga Salamero, Maria Belen Vidriales, Vadim Doronin, Hartmut Döhner, Amir T. Fathi, Eric Laille, Xin Yu, Maroof Hasan, Patricia Martin-Regueira, Courtney D. DiNardo
Přispěvatelé: Institut Català de la Salut, [de Botton S] Gustave Roussy, Université Paris-Saclay, Villejeuf, France. [Montesinos P] Hospital Universitari i Politecnic La Fe, Valencia, Spain. [Schuh AC] Princess Margaret Cancer Centre, Toronto, ON, Canada. [Papayannidis C] IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', Bologna, Italy. [Vyas P] Oxford Biomedical Research Centre and Oxford University Hospitals National Health Service Foundation Trust, Oxford, United Kingdom. [Wei AH] The Alfred Hospital, Melbourne, VIC, Australia. Monash University, Melbourne, VIC, Australia. [Salamero O] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Otros calificadores::/uso terapéutico [Otros calificadores]
Immunology
Genetic Phenomena::Genetic Variation::Mutation [PHENOMENA AND PROCESSES]
Medicaments antineoplàstics - Ús terapèutic
Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia
Myeloid::Leukemia
Myeloid
Acute [DISEASES]
Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores]
acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS]
Cell Biology
Hematology
Other subheadings::Other subheadings::/drug therapy [Other subheadings]
Biochemistry
neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mieloide aguda [ENFERMEDADES]
Anomalies cromosòmiques
Leucèmia mieloide aguda - Aspectes genètics
Leucèmia mieloide aguda - Tractament
Other subheadings::/therapeutic use [Other subheadings]
Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS]
fenómenos genéticos::variación genética::mutación [FENÓMENOS Y PROCESOS]
Zdroj: Scientia
Popis: Enasidenib; Conventional care Enasidenib; Atenció convencional Enasidenib; Atención convencional This open-label, randomized, phase 3 trial (NCT02577406) compared enasidenib, an oral IDH2 (isocitrate dehydrogenase 2) inhibitor, with conventional care regimens (CCRs) in patients aged ≥60 years with late-stage, mutant-IDH2 acute myeloid leukemia (AML) relapsed/refractory (R/R) to 2 or 3 prior AML-directed therapies. Patients were first preselected to a CCR (azacitidine, intermediate-dose cytarabine, low-dose cytarabine, or supportive care) and then randomized (1:1) to enasidenib 100 mg per day or CCR. The primary endpoint was overall survival (OS). Secondary endpoints included event-free survival (EFS), time to treatment failure (TTF), overall response rate (ORR), hematologic improvement (HI), and transfusion independence (TI). Overall, 319 patients were randomized to enasidenib (n = 158) or CCR (n = 161). The median age was 71 years, median (range) enasidenib exposure was 142 days (3 to 1270), and CCR was 36 days (1 to 1166). One enasidenib (0.6%) and 20 CCR (12%) patients received no randomized treatment, and 30% and 43%, respectively, received subsequent AML-directed therapies during follow-up. The median OS with enasidenib vs CCR was 6.5 vs 6.2 months (HR [hazard ratio], 0.86; P = .23); 1-year survival was 37.5% vs 26.1%. Enasidenib meaningfully improved EFS (median, 4.9 vs 2.6 months with CCR; HR, 0.68; P = .008), TTF (median, 4.9 vs 1.9 months; HR, 0.53; P < .001), ORR (40.5% vs 9.9%; P
Databáze: OpenAIRE
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