medwireNews: Rezvilutamide significantly delays disease progression and death relative to bicalutamide when each is combined with androgen deprivation therapy (ADT) in patients with high-volume metastatic, hormone-sensitive prostate cancer, research shows.
The preplanned interim analysis of the phase 3 CHART trial, which included patients from China, Poland, Czech Republic, and Bulgaria, “further validate[s] the clinical benefit of adding second-generation androgen receptor axis inhibitors to the ADT backbone” in these previously untreated patients, report Dingwei Ye (Shanghai Cancer Center, China) and co-authors in The Lancet Oncology.
They found that, after a median 21.2 months of follow-up, median radiographic progression-free survival (rPFS) was not reached in the 326 participants who were randomly assigned to receive the novel oral androgen receptor inhibitor rezvilutamide at a dose of 240 mg once daily in combination with ADT.
By comparison, median rPFS was 25.1 months among the 328 patients given bicalutamide 50 mg/day plus ADT, with the difference between the two groups corresponding to a significant 56% reduction in the risk for radiographic progression in favor of rezvilutamide.
At 2 years, the rPFS rate was 72.3% in the rezvilutamide group and 50.0% in the bicalutamide group.
Overall survival (OS) was assessed after a median 29.3 months of follow-up and was also significantly improved with rezvilutamide versus bicalutamide. Median OS was not reached in either group but statistical analyses showed that the risk for death was a significant 42% lower among patients who received rezvilutamide.
The 2-year OS rates were 81.6% and 70.3% in the rezvilutamide and bicalutamide arms, respectively.
The investigators note that rezvilutamide had a “tolerable safety profile,” with adverse event (AE) rates similar between the two treatment groups.
The median duration of treatment exposure was 28.9 months in the rezvilutamide group and 12.9 months in the bicalutamide group.
The most common grade 3 or worse treatment-emergent AEs were hypertension, occurring in 8% of 323 patients in the rezvilutamide group and 7% of 324 patients in the bicalutamide group, hypertriglyceridemia (7 vs 2%), increased weight (6 vs 4%), anemia (4 vs 5%), and hypokalemia (3 vs 1%).
Treatment-related serious AEs occurred in 4% and 3% of people who received rezvilutamide and bicalutamide, respectively.
No treatment-related deaths occurred in the rezvilutamide group and there was one, of unknown specific cause, in the bicalutamide group.
Ye et al conclude that their data “support the use of rezvilutamide in combination with ADT as a standard-of-care for patients with high-volume metastatic, hormone-sensitive prostate cancer.”
They add: “Future long-term analyses will be done to provide more evidence to verify the efficacy of rezvilutamide plus ADT in this patient population.”
In an accompanying comment, Louise Kostos and Declan Murphy, both from the Peter MacCallum Cancer Centre in Melbourne, Victoria, Australia, describe the OS benefit with rezvilutamide as “particularly impressive considering that the control group (bicalutamide plus ADT) was arguably more active than in previous similar trials (eg, the ARCHES and TITAN trials), which compared an androgen-receptor inhibitor plus ADT to ADT alone.”
They say: “Rezvilutamide will be a welcome addition to the range of androgen-receptor inhibitors already available, and will—we hope—through a little healthy competition, overcome some of the barriers to real-world use of doublet therapy, such as cost and access.”
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