Darolutamide + androgen deprivation therapy + docetaxel demonstrates consistent overall survival benefits across various patient segments in metastatic hormone-sensitive prostate cancer.- Bayer

Of the 1,306 mHSPC patients who were randomized, 79.5% had bone metastases (M1b) and 17.5% had visceral metastases (M1c); 55.5% had ALP greater than ULN. Extent of metastatic spread and ALP value are known prognostic factors in patients with mHSPC.

In the ARASENS trial , 1,306 patients were randomized 1:1 to receive darolutamide plus ADT and docetaxel or placebo plus ADT and docetaxel. Randomization was stratified by metastatic spread according to the most widely used cancer staging system, TNM (tumor, node, metastasis) classification: non-regional lymph node metastases only [M1a]; bone plus or minus lymph node metastases [M1b]; visceral plus or minus lymph node/bone metastases [M1c] and ALP value ( less then or greater than ULN at study entry). A consistent OS benefit was seen across the pre-specified subgroups with darolutamide plus ADT and docetaxel compared to ADT plus docetaxel, with a reduction in risk of death of 33% for subgroup M1b (hazard ratio [HR]=0.66, 95% CI 0.54–0.80) and 21% for M1c (HR=0.76, 95% CI 0.53–1.10). Subgroup M1a (n=39) was too small for meaningful comparison. For patients with ALP less than ULN, reduction in risk of death was 36% (HR=0.65, 95% CI 0.47–0.89) and 31% for patients with ALP greater than ULN (HR=0.69, 95% CI 0.56–0.85).These results add to existing data from the overall population in the ARASENS trial showing that darolutamide plus ADT and docetaxel significantly reduced the risk of death in patients with mHSPC by 32.5% (HR 0.68; 95% CI 0.57–0.80; P<0.001) compared to adt plus docetaxel.></0.001)>

Safety analyses showed that the rates of any-grade, grade 3–5, and serious AEs were similar for both arms in the overall population. The incidences of the most common treatment-emergent AEs (greater than 10%), the majority of which are known docetaxel-related AEs, were highest during the overlapping docetaxel treatment period in both arms.

“These favorable data from ARASENS in mHSPC, along with the ARAMIS data in non-metastatic castration-resistant prostate cancer (nmCRPC), reinforce the potential for darolutamide to be an optimal hormone therapy for eligible prostate cancer patients globally,” said Tara Frenkl, MD, MPH, Head of Oncology Development, Oncology Strategic Business Unit, Bayer. “We look forward to building on this body of evidence with future analyses from darolutamide’s clinical development program in metastatic hormone-sensitive prostate cancer.”

About the ARASENS Trial :The ARASENS trial is the only randomized, Phase III, multi-center, double-blind, trial which was prospectively designed to compare the use of a second-generation oral androgen receptor inhibitor (ARi) darolutamide in combination with docetaxel plus androgen deprivation therapy (ADT) to docetaxel plus ADT (a guideline recommended standard-of-care) in metastatic hormone-sensitive prostate cancer (mHSPC). A total of 1,306 newly diagnosed patients were randomized in a 1:1 ratio to receive 600 mg of darolutamide twice a day or matching placebo, in combination with docetaxel plus ADT. The primary endpoint of this trial was overall survival (OS). Secondary endpoints included time to castration-resistant prostate cancer (CRPC), time to pain progression, time to first symptomatic skeletal event (SSE), time to initiation of subsequent anticancer therapy, all evaluated at 12?week intervals, as well as adverse events (AEs) as a measure of safety and tolerability.