Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer
| Autor: | Smith, Matthew R, Hussain, Maha, Saad, Fred, Fizazi, Karim, Sternberg, Cora N, Crawford, E David, Kopyltsov, Evgeny, Park, Chandler H, Alekseev, Boris, Montesa-Pino, Álvaro, Dingwei, Ye, Parnis, Francis, Cruz, Felipe, Tammela, Teuvo L J, Suzuki, Hiroyoshi, Utriainen, Tapio, Cheng, Fu, Uemura, Motohide, Méndez-Vidal, María J, Maughan, Benjamin L, Joensuu, Heikki, Thiele, Silke, Rui, Li, Kuss, Iris, Tombal, Bertrand, Arasens, Investigators, Milella, Michele |
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| Přispěvatelé: | UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Aged
80 and over Male Neutropenia Prostatic Neoplasms Androgen Antagonists Antineoplastic Agents General Medicine Docetaxel Kaplan-Meier Estimate Middle Aged Castration-Resistant Prostatic Neoplasms Castration-Resistant Drug Therapy Combination Medicine and Health Sciences 80 and over Androgen Receptor Antagonists Humans Pyrazoles Drug Therapy Combination Neoplasm Metastasis Aged Proportional Hazards Models |
| Zdroj: | New England Journal of Medicine (International Edition), Vol. 386, no. 12, p. 1132-1142 (2022) NEW ENGLAND JOURNAL OF MEDICINE |
| ISSN: | 0028-4793 1533-4406 |
| Popis: | 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= 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, .) Darolutamide in Metastatic Prostate Cancer Standard therapy for metastatic, hormone-sensitive prostate cancer is androgen-deprivation therapy, usually with docetaxel. A large, multinational, phase 3 trial assessed the addition of the androgen-receptor blocker darolutamide to standard therapy. At 4 years, survival was higher with darolutamide than with placebo (62.7% vs. 50.4%), with no major differences in the frequency of adverse events. |
| Databáze: | OpenAIRE |
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