ARAMIS subgroup analysis: darolutamide benefits across PSADT groups

Prof. Martin Bögemann (University of Münster, Germany) presented a subgroup analysis of the ARAMIS trial (darolutamide vs placebo), which stratified patients into risk groups based on their prostate-specific antigen doubling time (PSADT), comparing safety and efficacy in patients with PSADTs of ≤6 months versus those with PSADTs >6-10 months [1,2]. Darolutamide demonstrated similar benefits in reducing metastases and death in both the PSADT ≤6 months and >6-10 months subgroups. The safety profile of the PSADT >6-10 months was similar to PSADT ≤6 months.

ARAMIS was a randomised, double-blind, placebo-controlled, phase 3 trial in men with non-metastatic castration-resistant prostate cancer (nmCRPC) and a PSADT of ≤10 months. Participants (n=1,509) received darolutamide or placebo while continuing androgen-deprivation therapy. The primary endpoint of metastasis-free survival was met [2]; moreover, with a median follow-up of 29 months, the ARAMIS final analysis reported that all key secondary endpoints were met as well [3]. A PSADT of ≤10 months was used to define patients at high risk for metastatic progression, which is associated with lower survival [4]. The current subgroup analysis assessed whether the PSADT value predicts response or safety signals of darolutamide.

To this end, the researchers grouped the trial arms into a presumably lower-risk category of PSADT >6-10 months (darolutamide n=286; placebo n=183), and higher-risk patients with PSADT ≤6 months (darolutamide n=669; placebo n = 371). Darolutamide reduced the risk of metastasis and death by 59% in the PSADT ≤6 months subgroup (HR 0.41; 95% CI 0.33-0.52) and 62% in the >6-10 months subgroup (HR 0.38; 95% CI 0.26-0.55), respectively, indicating equal efficacy across PSADTs [1]. Similarly, the safety profile of darolutamide was consistent across patients with PSADT >6-10 months and ≤6 months. Both groups showed a low incidence of adverse events (AEs) grade ≥3. The most frequently reported AEs in both subgroups were fatigue, back pain, and arthralgia. Minimal or no differences were observed in AEs characteristic for androgen receptor inhibitor treatment, such as falls, hypertension, and central nervous system-related events between darolutamide and placebo in both subgroups.

These results indicate that nmCRPC patients with PSADT >6-10 months can benefit from darolutamide without increased safety risks.

1. Bögemann M, et al. EAU20 Virtual Congress, 17-26 July 2020, Abstract 919.
2. Fizazi K, et al. N Engl J Med. 2019;380(13):1235-1246.
3. Fizazi K, et al. ASCO Virtual Meeting, 29-31 May 2020, Abstract 5514.
4. Smith MR, et al. J Clin Oncol. 2013;31(30):3800-3806.

Posted on 21 August 202017 May 2024