Overall survival was prolonged with the addition of darolutamide to androgen-deprivation therapy and docetaxel in patient with metastatic, hormone-sensitive prostate cancer.
Investigators reported significantly longer overall survival (OS) with the addition of darolutamide (Nubeqa) to androgen-deprivation therapy (ADT) and docetaxel (Taxotere) than with placebo, ADT, and docetaxel in patients with metastatic, hormone-sensitive prostate cancer.1
At the data cutoff date, the risk of death was 32.5% lower in the darolutamide group than in the placebo group (HR = .68; 95% CI, 0.57 to 0.80; P < .001). At 4 years, the OS for the treatment group was 62.7% (95% CI, 58.7%-66.7%) and 50.4% (95% CI, 46.3%-54.6%) for the placebo group.
Investigators of ARASENS (NCT02799602), a randomized, double-blind, placebo-controlled, phase 3 trial assigned 1306 patients 1:1 to receive darolutamide in 600 mg doses, twice a day, or placebo, both combined with (ADT) and docetaxel. The treatment group included of 651 patients, and the placebo group had 655 patients. The primary end point was OS, and the secondary end points were time to castration-resistant prostate cancer, time to pain progression, symptomatic skeletal event-free survival, and time to a first symptomatic skeletal event.
Median treatment duration was 41.0 months in the darolutamide group vs the placebo group, which had a median treatment duration of 16.7 months. At data cutoff, 45.9% of patients in the treatment arm were still receiving treatment compared with 19.1% of patients in the placebo arm. Time to castration-resistant disease was longer in the treatment arm (HR = 0.36; 95% CI, 0.30 to 0.42; P < .001) as well as time to pain progression (HR = 0.79; 95% CI, 0.66 to 0.95; P = .01). Median symptomatic skeletal event-free survival was 51.2 months in the darolutamide group vs 39.7 months in the placebo group (HR = .61; 95% CI, 0.52–0.72; P < .001).
Both groups displayed a similar rate of adverse events (AEs). Grade 3 or 4 adverse events occurred in 66.1% and 63.5% of darolutamide and placebo groups, respectively. The most common AEs reported were neutropenia, febrile neutropenia, hypertension, and anemia. Serious AEs occurred in 44.8% (n = 292) of the treatment arm and 42.3% (n = 275) of the placebo arm.
Findings from ARASENS are consistent with the PEACE-1 (NCT01957436) trial. PEACE-1, a phase 3 study for patients with metastatic hormone-naïve prostate cancer, results showed that overall survival improved with the addition of abiraterone (Zytiga) to ADT and docetaxel than ADT and docetaxel alone (HR = 0.75; 95% CI, 0.59-0.96).2
According to the investigators, these results support the use of darolutamide in combination with (ADT) and docetaxel in patients with metastatic, hormone-sensitive prostate cancer as both the primary and secondary end points showed improvement along with a similar safety profile.
1. Smith MR, Hussain M, Saad F, et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. Published online February 17, 2022. N Engl J Med. 2022;10.1056/NEJMoa2119115. doi:10.1056/NEJMoa2119115
2. Rydzewska LHM, Burdett S, Vale CL, et al. Adding abiraterone to androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis. Eur J Cancer. 2017;84:88-101. doi:10.1016/j.ejca.2017.07.003