• In the phase 3 PANTHER trial, EFS was similar between arms in the ITT population and in patients with higher-risk MDS

  • A signal for improved overall survival for pevonedistat plus azacitidine was seen in higher-risk MDS, especially with >3 treatment cycles

PANTHER was a global, randomized phase 3 trial of pevonedistat plus 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 20-30% blasts (n = 103). The primary endpoint was event-free survival (EFS). In the intent-to-treat (ITT) population median EFS was 17.7 months with pevonedistat plus azacitidine vs 15.7 months with azacitidine (hazard ratio [HR], 0.968 [95% confidence interval (CI), 0.757-1.238], P = 0.557) 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 = 0.431). Median overall survival (OS) in the higher-risk MDS cohort was 21.6 vs 17.5 months (HR, 0.785, P = 0.092]), and in patients with AML with 20-30% blasts was 14.5 vs 14.7 months (HR, 1.107, P = 0.664). 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 = 0.021) and for >6 cycles was 27.1 vs 22.5 months (P = 0.008). No new safety signals were identified, and 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 remaining on therapy >3 cycles. (ClinicalTrials.gov, NCT03268954).

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