Daralutamide and Survival in Metastatic, Hormone Sensitive Prostate Cancer

[Graham49]

Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer

List of authors.

Matthew R. Smith, M.D., Ph.D., Maha Hussain, M.D., Fred Saad, M.D., Karim Fizazi, M.D., Ph.D., Cora N. Sternberg, M.D., E. David Crawford, M.D., Evgeny Kopyltsov, M.D., Chandler H. Park, M.D., Boris Alekseev, M.D., Álvaro Montesa-Pino, M.D., Dingwei Ye, M.D., Francis Parnis, M.B., B.S., et al., for the ARASENS Trial Investigators*

Abstract

BACKGROUND

Darolutamide is a potent androgen-receptor inhibitor that has been associated with increased overall survival among patients with nonmetastatic, castration-resistant prostate cancer. Whether a combination of darolutamide, androgen-deprivation therapy, and docetaxel would increase survival among patients with metastatic, hormone-sensitive prostate cancer is unknown.

METHODS

In this international, phase 3 trial, we randomly assigned patients with metastatic, hormone-sensitive prostate cancer in a 1:1 ratio to receive darolutamide (at a dose of 600 mg [two 300-mg tablets] twice daily) or matching placebo, both in combination with androgen-deprivation therapy and docetaxel. The primary end point was overall survival.

RESULTS

The primary analysis involved 1306 patients (651 in the darolutamide group and 655 in the placebo group); 86.1% of the patients had disease that was metastatic at the time of the initial diagnosis. At the data cutoff date for the primary analysis (October 25, 2021), the risk of death was significantly lower, by 32.5%, in the darolutamide group than in the placebo group (hazard ratio 0.68; 95% confidence interval, 0.57 to 0.80; P<0.001). Darolutamide was also associated with consistent benefits with respect to the secondary end points and prespecified subgroups. Adverse events were similar in the two groups, and the incidences of the most common adverse events (occurring in ≥10% of the patients) were highest during the overlapping docetaxel treatment period in both groups. The frequency of grade 3 or 4 adverse events was 66.1% in the darolutamide group and 63.5% in the placebo group; neutropenia was the most common grade 3 or 4 adverse event (in 33.7% and 34.2%, respectively).

CONCLUSIONS

In this trial involving patients with metastatic, hormone-sensitive prostate cancer, overall survival was significantly longer with the combination of darolutamide, androgen-deprivation therapy, and docetaxel than with placebo plus androgen-deprivation therapy and docetaxel, and the addition of darolutamide led to improvement in key secondary end points. The frequency of adverse events was similar in the two groups. (Funded by Bayer and Orion Pharma; ARASENS ClinicalTrials.gov number, NCT02799602. opens in new tab.)

[joeguy]

I have been on Darolutimide for about 8 months, and so far I like it a lot better than the Xtandi I had taken previously....... far fewer side effects. I experimented with Darolutimide as a monotherapy for a few months, but after about 4 or 5 months, PSA began to rise and I had to add Orgovyx to the mix. So far I find the combo or Darolutimide, and Orgovyx very tolerable, and it appears to be lowering PSA.