Pevonedistat plus azacitidine vs azacitidine alone in higher-risk MDS/chronic myelomonocytic leukemia or low-blast-percentage AML
| Autor: | Lionel Adès, Larisa Girshova, Vadim A. Doronin, María Díez-Campelo, David Valcárcel, Suman Kambhampati, Nora-Athina Viniou, Dariusz Woszczyk, Raquel De Paz Arias, Argiris Symeonidis, Achilles Anagnostopoulos, Eduardo Ciliao Munhoz, Uwe Platzbecker, Valeria Santini, Robert J. Fram, Ying Yuan, Sharon Friedlander, Douglas V. Faller, Mikkael A. Sekeres |
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| Přispěvatelé: | Institut Català de la Salut, [Adès L] INSERM U944, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint Louis and University of Paris, Paris, France. [Girshova L] Federal Almazov North-West Medical Research Centre, Saint-Petersburg, Russia. [Doronin VA] City Clinical Hospital 40, Moscow, Russia. [Díez-Campelo M] Institute for Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, Salamanca, Spain. [Valcárcel D] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d'Hematologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Kambhampati S] Sarah Cannon at Research Medical Center, Kansas City, MO, Vall d'Hebron Barcelona Hospital Campus |
| Rok vydání: | 2022 |
| Předmět: |
acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::antimetabolitos::antimetabolitos antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS]
Antimetabolites Antineoplastic terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Antimetabolites::Antimetabolites Antineoplastic [CHEMICALS AND DRUGS] Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] Leukemia Myelomonocytic Chronic neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mielomonocítica crónica [ENFERMEDADES] Cyclopentanes Hematology Other subheadings::Other subheadings::/drug therapy [Other subheadings] Otros calificadores::Otros calificadores::/efectos adversos [Otros calificadores] Quimioteràpia combinada Medicaments antineoplàstics - Efectes secundaris Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia Myeloid::Leukemia Myelomonocytic Chronic [DISEASES] Pyrimidines Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Leucèmia mieloide aguda - Tractament Other subheadings::Other subheadings::/adverse effects [Other subheadings] Azacitidine Humans Drug Therapy Combination |
| Zdroj: | Scientia |
| ISSN: | 2473-9537 2473-9529 |
| DOI: | 10.1182/bloodadvances.2022007334 |
| Popis: | Pevonedistat; Chronic myelomonocytic leukemia Pevonedistat; Leucemia mielomonocítica crónica Pevonedistat; Leucèmia mielomonocítica crònica PANTHER is a global, randomized phase 3 trial of pevonedistat+azacitidine (n = 227) vs azacitidine monotherapy (n = 227) in patients with newly diagnosed higher-risk myelodysplastic syndromes (MDS; n = 324), higher-risk chronic myelomonocytic leukemia (n = 27), or acute myeloid leukemia (AML) with 20% to 30% blasts (n = 103). The primary end point was event-free survival (EFS). In the intent-to-treat population, the median EFS was 17.7 months with pevonedistat+azacitidine vs 15.7 months with azacitidine (hazard ratio [HR], 0.968; 95% confidence interval [CI], 0.757-1.238; P = .557) and in the higher-risk MDS cohort, median EFS was 19.2 vs 15.6 months (HR, 0.887; 95% CI, 0.659-1.193; P = .431). Median overall survival (OS) in the higher-risk MDS cohort was 21.6 vs 17.5 months (HR, 0.785; P = .092), and in patients with AML with 20% to 30% blasts was 14.5 vs 14.7 months (HR, 1.107; P = .664). In a post hoc analysis, median OS in the higher-risk MDS cohort for patients receiving >3 cycles was 23.8 vs 20.6 months (P = .021) and for >6 cycles was 27.1 vs 22.5 months (P = .008). No new safety signals were identified, and the azacitidine dose intensity was maintained. Common hematologic grade ≥3 treatment emergent adverse events were anemia (33% vs 34%), neutropenia (31% vs 33%), and thrombocytopenia (30% vs 30%). These results underscore the importance of large, randomized controlled trials in these heterogeneous myeloid diseases and the value of continuing therapy for >3 cycles. The trial was registered on clinicaltrials.gov as #NCT03268954. This study was sponsored by Takeda Development Centers Inc (TDCA; Lexington, MA). |
| Databáze: | OpenAIRE |
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