KEY TAKEAWAYS
- PANTHER is a randomized, global Phase 3 clinical trial that compared pevonedistat+azacitidine vs. azacitidine monotherapy in patients with newly diagnosed higher-risk MDS, CMML, or AML with 20-30% blasts.
- The primary endpoint of this study was EFS, with a median EFS of 17.7 months in the pevonedistat+azacitidine group vs. 15.7 months in the azacitidine group (HR 0.968; 95% CI 0.757-1.238; p = 0.557).
- Common hematologic grade ≥3 treatment-emergent AEs included anemia (33% vs. 34%), neutropenia (31% vs. 33%), and thrombocytopenia (30% vs. 30%).
- Post-hoc analysis indicated that the median OS increased with more cycles of therapy, with a median OS of 23.8 months in the higher-risk MDS cohort for patients receiving >3 cycles vs. 20.6
Patients with newly diagnosed higher-risk myelodysplastic syndromes (MDS; n = 324), higher-risk chronic myelomonocytic leukemia (n = 27), or acute myeloid leukemia (AML; n = 103) were randomly assigned to receive either pevonedistat+azacitidine (n = 227) or azacitidine monotherapy (n = 227) in a global, randomized phase 3 trial called PANTHER. The key outcome measure was time to a first adverse event (EFS). Median event-free survival (EFS) was more prolonged with pevonedistat+azacitidine (HR, 0.968; 95% CI, 0.757-1.238; P =.557) in the intent-to-treat group compared to azacitidine alone (15.7 months vs. 19.2 months; HR, 0.887; 95% CI, 0.659-1.193; P =.431).
Patients with AML having 20% to 30% blasts had a median OS of 14.5 months compared to 14.7 months (HR, 1.107; P =.664), while those with higher-risk MDS had a median OS of 21.6 months compared to 17.5 months (HR, 0.785; P =.092). Median overall survival (OS) in the higher-risk MDS sample was 23.8 vs. 20.6 months for patients who received >3 cycles of treatment (P =.021) and 27.1 vs. 22.5 months for those who received >6 cycles of treatment (P =.008). The same level of azacitidine was used since no additional safety signals were detected. Anemia (33% vs. 34%), neutropenia (31% vs. 33%), and thrombocytopenia (30% vs. 30%) were the most common hematologic grade ≥3 treatment-emergent adverse events. Our findings demonstrate the efficacy of maintaining treatment for more than three cycles in patients with these various myeloid disorders. Clinicaltrials.gov confirmed the trial’s enrollment.
Source: https://pubmed.ncbi.nlm.nih.gov/35728048/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03268954
Adès L, Girshova L, Doronin VA, Díez-Campelo M, Valcárcel D, Kambhampati S, Viniou NA, Woszczyk D, De Paz Arias R, Symeonidis A, Anagnostopoulos A, Munhoz EC, Platzbecker U, Santini V, Fram RJ, Yuan Y, Friedlander S, Faller DV, Sekeres MA. Pevonedistat plus azacitidine vs. azacitidine alone in higher-risk MDS/chronic myelomonocytic leukemia or low-blast-percentage AML. Blood Adv. 2022 Sep 13;6(17):5132-5145. doi 10.1182/bloodadvances.2022007334. PMID: 35728048; PMCID: PMC9631625.
