Apalutamide for Metastatic Castration-Sensitive Prostate Cancer

[Balsam01]

TAKE-HOME MESSAGE

•The authors of this double-blind, phase III trial randomly assigned 525 patients with metastatic, castration-sensitive prostate cancer to receive apalutamide or placebo, added to ADT. The study allowed for previous treatment for localized disease and previous docetaxel therapy. The radiographic progression–free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (HR for radiographic progression or death, 0.48). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% vs 73.5%, respectively; HR, 0.67).

•Adding apalutamide to ADT offered patients with metastatic, castration-sensitive prostate cancer improved overall survival and radiographic progression-free survival when compared with patients receiving ADT plus placebo.

– Jeffrey Wiisanen, MD

Background:

Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression–free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined.

Methods

In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression–free survival and overall survival.

Results:

A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression–free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P=0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group.

Conclusions:

In this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression–free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups.

The New England Journal of Medicine.

Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer

N. Engl. J. Med 2019 May 31;[EPub Ahead of Print], KN Chi, N Agarwal, A Bjartell, et al

[6357axbz]

Each time I read about this trial I ask how does apalutimide/ADT compare to using abiraterone/ADT for mHSPCa?

[tallguy2]

This is excellent. Thanks for posting this. I will put this topic on my list for my August 2 appointment.