Darolutamide added to existing combination therapy in metastatic prostate cancer increases survival, NEJM says

In a new trial overall survival was remarkably longer with the combination of darolutamide, androgen-deprivation therapy, and docetaxel than with placebo plus androgen-deprivation therapy and docetaxel, involving patients with metastatic, hormone-sensitive prostate cancer, and the addition of darolutamide led to improvements in key secondary endpoints.

Darolutamide is a strong androgen-receptor inhibitor that has been linked to improved overall survival in nonmetastatic, castration-resistant prostate cancer patients. Therefore, this study was conducted by Matthew R. Smith and team with the objective to see if a combination of darolutamide, androgen deprivation treatment, and docetaxel would improve survival in individuals with hormone-sensitive prostate cancer who have progressed. The findings of this study were published in The New England Journal of Medicine.

In this phase 3 study, patients with metastatic hormone-sensitive prostate cancer were randomly allocated in a 1:1 ratio to receive darolutamide (600 mg [two 300-mg tablets] twice daily) or a matched placebo, both in conjunction with androgen restriction treatment and docetaxel. Overall survival was the major goal.

The key findings of this study is as follow:

1. The primary study included 1306 individuals (651 darolutamide patients and 655 placebo patients); 86.1% of the patients had metastatic illness at the time of diagnosis.

2. The risk of mortality in the darolutamide group was 32.5% lower than in the placebo group at the data cutoff date for the primary analysis (October 25, 2021) (hazard ratio 0.68; 95% confidence range, 0.57 to 0.80; P0.001).

3. Darolutamide was also linked to consistent improvements in terms of secondary endpoints and predetermined subgroups.

4. Adverse events were comparable in both groups, with the most prevalent adverse effects (which occurred in 10% of patients) happening more often during the overlapped docetaxel treatment period in both groups.

5. The darolutamide group had 66.1% of grade 3 or 4 adverse events, whereas the placebo group had 63.5 percent; neutropenia was the most prevalent grade 3 or 4 adverse event (in 33.7% and 34.2% , respectively).

In conclusion, the findings of this study clearly points out the efficiency of the combination therapy against prostate cancer and it should be employed more often in the concerned area.

Reference: 

Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED, Kopyltsov E, Park CH, Alekseev B, Montesa-Pino Á, Ye D, Parnis F, Cruz F, Tammela TLJ, Suzuki H, Utriainen T, Fu C, Uemura M, Méndez-Vidal MJ, Maughan BL, Joensuu H, Thiele S, Li R, Kuss I, Tombal B; ARASENS Trial Investigators. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022 Feb 17. doi:10.1056/NEJMoa2119115. Epub ahead of print. PMID: 35179323.