Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer

[Balsam01]

From Practice Update. I would appreciate some feedback as to whether the members have already seen these articles that I post from Practice Update. I assume most people already subscribe to Practice Update? I don't want to unnecessarily waste bandwidth.

practiceupdate.com/C/79887/56

[Tall_Allen]

Yes, I've seen it, but so what? Maybe someone hasn't and threads quickly vanish, so re-posting won't hurt. Go ahead, waste the bandwidth!

[Balsam01 in reply to Tall_Allen]

TAKE-HOME MESSAGE

•In this randomized phase III trial involving 1509 men with nonmetastatic, castration-resistant prostate cancer and a PSA doubling time of ≤10 months, the authors evaluated the efficacy of darolutamide compared with placebo for delaying metastasis and death. The median metastasis-free survival was 40.4 months with darolutamide versus 18.4 months with placebo (P<.001). In addition, darolutamide showed benefits over placebo for overall survival, time to pain progression, time to cytotoxic chemotherapy, and time to a symptomatic skeletal event. Rates of adverse events and treatment discontinuation due to adverse events were similar in the two groups.

•The use of darolutamide is associated with longer metastasis-free survival compared with placebo among men with nonmetastatic, castration-resistant prostate cancer without increasing the risk of adverse events.

– Jeffrey M. Wiisanen, MD

abstract

This abstract is available on the publisher's site.

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BACKGROUND

Darolutamide is a structurally unique androgen-receptor antagonist that is under development for the treatment of prostate cancer. We evaluated the efficacy of darolutamide for delaying metastasis and death in men with nonmetastatic, castration-resistant prostate cancer.

METHODS

We conducted a randomized, double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic, castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned in a 2:1 ratio to receive darolutamide (600 mg [two 300-mg tablets] twice daily) or placebo while continuing androgen-deprivation therapy. The primary end point was metastasis-free survival, with the presence of metastasis determined by independent central review of radiographic imaging every 16 weeks.

RESULTS

In total, 1509 patients underwent randomization (955 to the darolutamide group and 554 to the placebo group). In the planned primary analysis, which was performed after 437 primary end-point events had occurred, the median metastasis-free survival was 40.4 months with darolutamide, as compared with 18.4 months with placebo (hazard ratio for metastasis or death in the darolutamide group, 0.41; 95% confidence interval, 0.34 to 0.50; P<0.001). Darolutamide was also associated with benefits with regard to all secondary end points, including overall survival, time to pain progression, time to cytotoxic chemotherapy, and time to a symptomatic skeletal event. The incidence of adverse events that occurred or worsened during the treatment period and had a frequency of 5% or more or were of grade 3 or higher was similar in the two groups; all such events except fatigue occurred in less than 10% of patients in either group. The percentage of patients who discontinued the assigned regimen because of adverse events was 8.9% in the darolutamide group and 8.7% in the placebo group. Darolutamide was not associated with a higher incidence of seizures, falls, fractures, cognitive disorder, or hypertension than placebo.

CONCLUSIONS

Among men with nonmetastatic, castration-resistant prostate cancer, metastasis-free survival was significantly longer with darolutamide than with placebo. The incidence of adverse events was similar for darolutamide and placebo.

[Twoofus]

Keep posting their information, most is very good and I don’t mind reading it twice if I have forgotten what I read the first time.

[cujoe]

I'm with Twoofus! Thanks, as not everyone spends their entire day monitoring posts here and can easily miss important info relevant to their situation. Be Well - cujoe

[cfrees1]

Does anyone know if this would be a viable "next treatment" if my PSA starts to increase on Apalutamide? I don't quite understand how failing one "...amide" type drug impacts the others in that family? Does anyone know?