Pevonedistat plus azacitidine vs azacitidine alone in higher-risk MDS/chronic myelomonocytic leukemia or low-blast-percentage AML
Year: 2022
Type: article
Study design: Clinical Trial
Abstract: 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.
Source: Blood Advances
Authors: 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
Institutions: Inserm, Université Paris Cité, Génomes, biologie cellulaire et thérapeutiques, Assistance Publique – Hôpitaux de Paris, Hôpital Saint-Louis, Federal Almazov North-West Medical Research Centre, City Clinical Hospital, Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, Research Medical Center, National and Kapodistrian University of Athens, Laiko General Hospital of Athens, University of Opole, Hospital Universitario La Paz, General University Hospital of Patras, G. Papanikolaou General Hospital, Hospital Erasto Gaertner, University Hospital Leipzig, Azienda Ospedaliero-Universitaria Careggi, University of Florence, University of Miami, Sylvester Comprehensive Cancer Center
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,000
Funder: Takeda Pharmaceuticals U.S.A.
OpenAlex ID: W4283264931