Rapid Readout: ARASENS: Darolutamide Versus Placebo in Combination With ADT and Docetaxel for Metastatic Hormone-Sensitive Prostate Cancer

OncLive® Rapid Readout from Overall Survival With Darolutamide Versus Placebo in Combination With Androgen-Deprivation Therapy and Docetaxel for Metastatic Hormone-Sensitive Prostate Cancer in the Phase 3 ARASENS Trial

Segment Description: Alan H. Bryce, MD, discusses the ARASENS trial, as presented at The American Society of Clinical Oncology Genitourinary Cancers Symposium in February 2022.

Segment Body Content:

• Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor inhibitor that demonstrated improved overall survival (OS) and metastasis-free survival vs placebo (PBO) and a low incidence of treatment-emergent adverse events (TEAEs) in patients with nonmetastatic castration-resistant prostate cancer (CRPC).
• We investigated whether DARO in combination with standard androgen-deprivation therapy (ADT) + docetaxel would increase OS in pts with metastatic hormone-sensitive prostate cancer (mHSPC) in the ARASENS study (NCT02799602).

Methods

• This international, double-blind, phase 3 study enrolled patients with mHSPC and ECOG PS 0/1 who were randomized 1:1 to DARO 600 mg twice daily or matching PBO in addition to ADT + docetaxel. Randomization was stratified by extent of disease according to TNM (M1a vs M1b vs M1c) and alkaline phosphatase levels (< vs ≥ upper limit of normal).
• The primary endpoint was OS. Secondary efficacy endpoints included time to CRPC, time to pain progression, time to first symptomatic skeletal event (SSE), and time to initiation of subsequent systemic antineoplastic therapies. Safety was also assessed.

Results

• From Nov 2016 to June 2018, 1306 patients were randomized, 651 to DARO and 655 to PBO, in combination with ADT + docetaxel. Median age was 67 years in both arms.
• At the primary data cutoff (Oct 25, 2021), DARO significantly decreased the risk of death by 32.5% vs PBO (HR 0.675, 95% CI 0.568–0.801; P < 0.0001). The significant improvement in OS was observed even though substantially more patients received subsequent life-prolonging systemic antineoplastic therapy in the PBO arm (75.6%) vs the DARO arm (56.8%). The significant OS benefit was consistent across prespecified subgroups.
• In addition, DARO significantly delayed time to CRPC vs PBO (HR 0.357, 95% CI 0.302–0.421; P < 0.0001). Time to pain progression was also significantly longer with DARO vs PBO (HR, 0.792, 95% CI 0.660–0.950; P = 0.0058), as were time to first SSE and time to initiation of subsequent systemic antineoplastic therapy.
• TEAEs were similar between treatment arms, and the incidences of the most common TEAEs (≥ 10%) were highest during the overlapping docetaxel treatment period for both arms, with grade 3/4 TEAEs of 66.1% for DARO and 63.5% for PBO, mainly due to neutropenia (33.7% vs 34.2%, respectively). TEAEs led to treatment discontinuation in 13.5% of patients in the DARO arm and 10.6% of patients in the PBO arm.

Conclusions

• In patients with mHSPC, early treatment combining DARO with ADT + docetaxel significantly increased OS and improved key secondary endpoints vs ADT + docetaxel alone. The incidence of TEAEs was similar in the two treatment arms.