Research Frontier ARAMIS trial results update: treatment of nmCRPC patients, darolutamide can be expected in the future!

Patients with prostate-specific antigen doubling time (PSADT) ≤ 10 months of non-metastatic castration-resistant prostate cancer (nmCRPC) are at
high risk of disease progression and metastasis.
Recently, the results of an important subgroup analysis of the phase III ARAMIS trial were announced, what is the efficacy and safety of darolutamide in this type of patient? The editor has compiled the following for the reader
.

Evidence suggests that shorter PSADT predicts a higher risk of disease progression and metastasis
.
PSADT<6 months is generally considered the cut-off for patients to receive more aggressive therapy, and international evidence-based guidelines recommend that patients with PSADT ≤ 10 months should be treated<b11> with standard androgen deprivation therapy (ADT) plus a new-generation androgen receptor inhibitor (ARI).
Therefore, the ARAMIS trial stratified patients with nmCRPC according to PSADT (PSADT≤ 6 months; 6< PSADT ≤10 months) to assess the efficacy and safety<b12> of darolutamide compared to placebo in different subgroups of patients with PSADT.

ARAMIS (NCT02200614) is a global, multicenter, double-blind, randomized phase III trial in patients with nmCRPC with PSADT ≤ 10 months
.
Patients were randomized 2:1 to darolutamide and placebo and received ADT + darolutamide (600 mg orally twice daily) and ADT+ placebo
, respectively.
The primary endpoint was metastasis-free survival (MFS), and the secondary endpoints were overall survival (OS), time to pain progression, time to first chemotherapy administration, and time to first symptomatic skeletal event (SSE), while quality of life (QoL) and safety
were also assessed.

Of the 1509 enrolled patients, 469 had PSADT > 6 months (n=286 in the darolutamide group; n=183 in the placebo group) and PSADT ≤ 6 months in 1040 patients (n=669 in the darolutamide group; n=371 in the placebo group).

The baseline characteristics of patients were approximately the same between the
two subgroups.

Compared with placebo, darolutamide significantly prolonged the patient's MFS
.
In the PSADT > 6-month group, the risk of disease metastasis or death was significantly reduced by 62% (HR = 0.
38, 95% CI 0.
26 to 0.
55); In the PSADT ≤ 6-month group, the risk of disease metastasis or death was reduced by 59% (HR = 0.
41, 95% CI 0.
33 to 0.
52).

Figure 1 Kaplan-Meier survival curve of MFS and OS for subgroups by PSADT

Compared to placebo, darolutamide significantly prolonged the patient's OS
.
The risk of death was reduced by 45% in the PSADT>6-month group (p=0.
01) compared with 26% (p=0.
04)
in the PSADT≤6-month group.

Other efficacy endpoints (time to pain progression, time to first chemotherapy, SSE, and progression-free survival) and QoL endpoint analysis showed significant improvement
in patients treated with darolutamide in both subgroups compared with placebo.
Patients had a lower incidence of treatment-related adverse events (including ADT-related adverse events or discontinuation due to adverse events), and darolutamide was similar
to placebo in terms of safety outcomes.

Darolutamide showed good efficacy and tolerability in patients with nmCRPC >at 6 months (≤ 10 months) of PSADT, significantly improved MFS, OS, and other clinically relevant outcomes, and maintained QoL
.

References:

Bögemann M, Shore ND, Smith MR, et al.
Efficacy and Safety of Darolutamide in Patients with Nonmetastatic Castration-resistant Prostate Cancer Stratified by Prostate-specific Antigen Doubling Time: Planned Subgroup Analysis of the Phase 3 ARAMIS Trial.
Eur Urol.
2022 Sep 8:S0302-2838(22)02532-5.
doi: 10.
1016/j.
eururo.
2022.
07.
018.
Epub ahead of print.
PMID: 36089529.