Search

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.

Background: Complete resection and pre-/peri-/post-operative chemotherapy are the standard of care for patients with stage IV CRC and resectable metastases confined to the liver. Despite this treatment approach, long-term disease-free survival of patients with resected liver metastases is poor. The oral multikinase inhibitor REG significantly improved overall survival (OS) in patients with metastatic CRC that had progressed after all standard therapies (CORRECT study; HR 0.77; one-sided p = 0.0052; Lancet 2013). COAST will evaluate the efficacy and safety of REG vs PBO in patients with CRC after curative resection of liver metastases and completion of planned chemotherapy. Trial design: This double-blind, PBO-controlled, multicenter, phase III study (ClinicalTrials.gov identifier NCT01939223) will randomize patients (n = 750 planned) 1 : 1 to treatment with oral REG 160 mg or PBO once daily in 4-week cycles of 3 weeks on, 1 week off treatment. Doses of study drug may be delayed or reduced to manage clinically significant drug-related toxicities. Treatment will continue for 2 years or until recurrence of CRC, death, intolerable toxicity, or patient/investigator decision to stop. Inclusion criteria include age ≥18 years, stage IV CRC, pathology-proven complete resection of liver metastases, and ECOG performance status 0 or 1. Patients must have completed adjuvant, neoadjuvant, or perioperative chemotherapy. Randomization will be stratified by number of preoperative liver metastases ( 6 months), and time since last surgery for any CRC lesion (≤6 months vs >6 months). The primary endpoint is disease-free survival (DFS), assessed by the investigator using computed tomography or magnetic resonance imaging. Secondary endpoints include OS, health-related quality of life, and biomarker evaluations. Analyses will be performed when approximately 317 DFS events are observed, at which time the study will have 90% power to detect a 50% improvement in median DFS. The first patient entered the study in February 2014 and the estimated primary completion date is March 2018.Previously presented at WCGI 2014 abstract number: 749 (to be presented at WCGI 2014 as a poster presentation). Disclosure: A. Grothey: has the following financial disclosures: Advisory board: Bayer Corporate sponsored research: Bayer, Genentech, Eisai, Pfizer, ImClone, Daiichi; T. Yoshino: has the following financial disclosures: Corporate sponsored research: Daiichi Sankyo, Taiho, Bayer, Eli Lilly, Pfizer, Chugai, and Yakult; J. Zalcberg: has the following financial disclosures: Advisory board: Bayer, Roche Research and travel support, expert testimony: Bayer, Roche; D.J. Sargent: has the following financial disclosures: Advisory board: Bayer, Roche Corporate sponsored research: Roche, Celgene; M. Choti: has the following financial disclosures: Research consultant: Bristol Myers Squibb; M. Rutstein: has the following financial disclosures: Employment: Bayer HealthCare; L. Cupit: has the following financial disclosures: Employment: Bayer; I. Kuss: has the following financial disclosures: Employment: Bayer Pharma AG; E. Van Cutsem: has the following financial disclosures: Corporate sponsored research: Bayer . All other authors have declared no conflicts of interest.