PANTHER Trial Compares Pevonedistat Plus Azacitidine vs Azacitidine Alone in MDS, AML

A global, phase III trial comparing pevonedistat plus azacitidine versus azacitidine alone in three groups of patients with different myeloid diseases underscored the value of large, controlled studies in this group of patients and the value of remaining on therapy for more than three years, according to the investigators.

The phase III PANTHER trial investigated pevonedistat plus azacitidine (n=227) versus azacitidine monotherapy (n=227) in higher-risk myelodysplastic syndromes ([MDS]; n=324), higher-risk chronic myelomonocytic leukemia ([CMML]; n=27), and acute myeloid leukemia ([AML] with 20% to 30% blasts (n=103).

The primary endpoint was event-free survival (EFS), defined as time from randomization to death or transformation to AML (requiring a 50% increase or more in blasts to at least 20% blasts) in patients with higher-risk MDS/CMML, whichever occurred first, or time to death in patients with AML with 20% to 30% blasts. The key secondary endpoint was overall survival (OS).

In the intent-to-treat (ITT) population, median EFS was 17.7 months with pevonedistat plus azacitidine versus 15.7 months with azacitidine (hazard ratio [HR], 0.968; 95% CI, 0.757-1.238; P=.557). In the higher-risk MDS cohort, median EFS was 19.2 versus 15.6 months (HR, 0.887; 95% CI, 0.659-1.193; P=.431).

Median OS in the higher-risk MDS cohort was 21.6 versus 17.5 months (HR, 0.785; P=.092) and in patients with AML with 20% to 30% blasts was 14.5 versus 14.7 months (HR, 1.107; P=.664). In a post-hoc analysis, median OS in the higher-risk MDS cohort for patients receiving more than three cycles was 23.8 versus 20.6 months (P=.021) and for more than six cycles was 27.1 versus 22.5 months (P=.008).

The investigators, led by Lionel Adès, MD, PhD, of the Hôpital Saint-Louis in Paris, France, published their findings in Blood Advances.

“These results underscore the importance of large, randomized controlled trials in these heterogeneous myeloid diseases and the value of remaining on therapy [more than three] cycles,” the authors concluded.

Adès L, Girshova L, Doronin VA, et al. Pevonedistat plus azacitidine vs azacitidine alone in higher-risk MDS/chronic myelomonocytic leukemia or low-blast percentage AML. Blood Adv. 2022. doi:10.1182/bloodadvances.2022007334