Preface
In the phase III ARASENS study, the efficacy of darolutamide (DARO) in combination with androgen deprivation therapy (ADT) and docetaxel (DOC) in metastatic hormone-sensitive prostate cancer (mHSPC) has received extensive attention from the medical community. Recently, European Urology, the top journal in the field of urology, published updated results of the trial, showing that compared with placebo (PBO), the darolutamide triple regimen achieved a deep and durable PSA response in patients with mHSPC.
Background:
Results from the global Phase III ARASENS study (NCT02799602) showed that the combination of DARO+ADT+DOC significantly improved overall survival (OS) in patients with mHSPC compared with PBO with a favorable safety profile. mHSPC can rapidly progress to castration-resistant disease with reduced survival. Identifying potential predictors of progression can better guide treatment strategies in clinical practice, and prostate-specific antigen (PSA) has become a well-established tool for prostate cancer screening, diagnosis, and treatment monitoring. Previous studies have shown that reduced PSA to undetectable levels (≤0.2 ng/ml) in patients with mHSPC is associated with better clinical outcomes, including overall survival (OS). Based on this, the ARASENS study investigated the remission effect of the DARO triple regimen on PSA and its correlation with the clinical outcomes of patients with high/low burden mHSPC in an exploratory analysis.
Research Methods:
ARASENS is an international, double-blind, phase III study in which patients with mHSPC are randomized in a 1:1 ratio to receive DARO (600 mg, bid, n=651) + ADT + DOC or PBO (n=654) + ADT + DOC. The unmeasurable rate of PSA (<0.2 ng/mL) and time to PSA progression (25% PSA elevation from ≥baseline and absolute PSA ≥2 ng/ml) were included in the prespecified exploratory analysis. PSA outcomes by disease burden and associations between PSA undetectability rate and OS, time to castration-resistant prostate cancer (CRPC) and time to PSA progression were assessed in post-hoc analyses.
Findings:
● At any time from the start of treatment to the data cut-off on October 25, 2021, the undetectable rate of PSA in the DARO group more than doubled compared to the PBO group:
In the overall population: 67 versus 29 percent, high-burden subgroup: 62 versus 26 percent, low-burden subgroup: 84 versus 38 percent
Table 1 Temporal changes in the undetectable rate of PSA in the total population and disease burden subgroups
● Compared with PBO, DARO delays the time to PSA progression in patients with mHSPC:
总体人群中：HR=0.26（95%CI 0.21-0.31）；高负荷亚组：HR=0.30（95%CI 0.24-0.37）；低负荷亚组：HR=0.093（95%CI 0.047-0.18）
Fig. 1 (A) overall population and (B) time to PSA progression in the disease burden subgroup
●The unmeasurable rate of PSA at 24 weeks was associated with longer OS (HR = 0.49, 95% CI 0.37-0.65), time to CRPC, and time to PSA progression in the DARO group, with a consistent trend in the disease burden subgroup.
Conclusions of the study
Overall, the DARO triple regimen achieved deep and durable PSA remission in patients with high/low burden mHSPC, and PSA reduction to undetectable levels was associated with better clinical outcomes (OS, time to CRPC, time to PSA progression).
Bibliography:
[1] Saad F, Hussain MHA, Tombal B, et al. Deep and Durable Prostate-specific Antigen Response to Darolutamide with Androgen Deprivation Therapy and Docetaxel, and Association with Clinical Outcomes for Patients with High- or Low-volume Metastatic Hormone-sensitive Prostate Cancer: Analyses of the Randomized Phase 3 ARASENS Study. Eur Urol. Published online April 20, 2024.
编辑:Gardenia审校:Gardenia执行:Gardenia
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