Practice-changing study for this specific patient population (see inclusion criteria) with approximately 30% risk reduction of death with excellent tolerability of treatment arm of this study.
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.
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.
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).
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.)
Less radiation is non-inferior, this is for low and intermediate-risk localized prostate cancer patients. Would like input from our radiation oncologists as to whether or not this adoptable?
Protons vs IMRT for localized prostate cancer showed no difference in outcome or quality of life. There will be longer f/u and other endpoints studied but the take-home message is that protons are not significantly better than photons.
Will we be replaced by AI? It seems that for radiologists, an AI system was better than the human counterpart in this study looking at prostate cancer diagnostic imaging. I doubt many of us would accept a solely computer-generated report, but this study highlights how AI may help as a supportive tool in the primary diagnostic setting. Of course, prospective validation will be needed.
10-year metastasis-free survival was 71.9% in the short-course ADT group (6 months) and 78% in the long-course ADT group (24 months). So, it seems the longer the duration, the better the outcome. 93% had a Gleason score of 7 or higher.
We know that combination PARP and antiandrogen is better than antiandrogen alone. I have wondered if we need antiancrogen on those patients. This shows that, YES, we do. The combination also was better than PARP inhibitor monotherapy in those patients carrying HRRm.
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