KEY TAKEAWAYS
- The phase 3 ARASENS study evaluated the efficacy and safety of combining DARO with ADT and docetaxel in mHSPC.
- The trial’s primary endpoint was to evaluate OS with secondary endpoints, including monitoring the time to CRPC and safety.
- The study demonstrated that the benefits and safety dynamics of DARO, compared to a placebo, remained consistent among the NA pts.
In the ARASENS study, the combination of darolutamide (DARO), androgen-deprivation therapy (ADT), and docetaxel significantly lowered death risk by 32.5% (HR 0.68, 95% CI 0.57–0.80; P<0.0001) when compared to a placebo (PBO) with ADT and docetaxel for patients with metastatic hormone-sensitive prostate cancer (mHSPC). DARO maintained life quality, offering similar control over disease-associated physical symptoms and pain as the placebo, and exhibited a favorable safety profile.
In this double-blind, phase 3 trial, participants were evenly randomized to either DARO 600 mg taken twice daily or a placebo in conjunction with ADT and docetaxel. The key objective was to evaluate overall survival (OS), with significant secondary goals including monitoring the time to castration-resistant prostate cancer (CRPC) and safety.
Out of the 1305 participants assessed, 244 (18.7%) were from North America (218 from the US, 26 from Canada, 125 for DARO, and 119 for PBO). Among these, 36 (14.8%) identified as Black/African American. The baseline attributes of the NA participants largely mirrored the global group, with the exception of the percentage having de novo metastatic disease (75.8% in NA vs 86.1% globally). For NA participants, the DARO + ADT + docetaxel combination showed more favorable OS outcomes compared to the PBO combination (HR 0.59, 95% CI 0.39–0.89), with a 4-year survival rate comparison of 66% to 50%. The DARO group also demonstrated a prolonged time to CRPC (HR 0.32, 95% CI 0.21–0.48). DARO’s safety characteristics among NA participants aligned with the global group’s findings (grade 3/4 treatment-related adverse events [TEAEs] were 61% in NA vs 66% globally; serious TEAEs were 44% in NA vs 45% globally). The frequency of TEAEs linked to androgen receptor pathway obstruction was relatively consistent for both DARO and PBO, especially when adjusted for the treatment period. The OS advantage and safety dynamics of DARO compared to PBO were also observed in Black/African American participants, aligning with the global group.
For North American patients with mHSPC, incorporating DARO into the ADT + docetaxel regimen resulted in a noteworthy 41% reduction in death risk and extended the patient-relevant secondary endpoint of time to CRPC. The occurrence rates of TEAEs in NA patients were fairly consistent between the treatment groups and paralleled the findings in the global group.
Source: https://www.auajournals.org/doi/10.1097/JU.0000000000003257.02
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT02799602
Shore, Neal D.; Tombal, Bertrand; Hussain, Maha; Saad, Fred; Fizazi, Karim; Sternberg, Cora N.; Crawford, E. David; Nordquist, Luke; Tutrone, Ronald; Belkoff, Laurence; Kapur, Shivani; Jhaveri, Jay; Srinivasan, Shankar; Joensuu, Heikki; Smith, Matthew R. MP29-02 EFFICACY AND SAFETY OF DAROLUTAMIDE IN COMBINATION WITH ANDROGEN-DEPRIVATION THERAPY AND DOCETAXEL IN THE NORTH AMERICAN POPULATION FROM ARASENS, Journal of Urology: April 2023 – Volume 209 – Issue Supplement 4 doi: 10.1097/JU.0000000000003257.02
