Darolutamide Maintenance in Patients With Metastatic Castration-Resistant Prostate Cancer Without Disease Progression on Taxane Treatment

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In a European phase II trial (Swiss Group for Clinical Cancer Research [SAKK] 08/16) reported in the Journal of Clinical Oncology, Silke Gillessen, MD, and colleagues found that darolutamide maintenance improved progression-free survival vs placebo in patients with metastatic castration-resistant prostate cancer who had received prior androgen receptor pathway inhibitor treatment and subsequently had nonprogressive disease on taxane therapy.

Silke Gillessen, MD

Silke Gillessen, MD

Study Details

In the trial, 90 patients from sites in France, Italy, Spain, and Switzerland were randomly assigned between April 2017 and November 2020 to receive maintenance darolutamide at 600 mg twice a day (n = 45) or placebo twice a day (n = 45); treatment continued until disease progression or unacceptable toxicity. Prior taxane treatment consisted of docetaxel in 93% of patients and cabazitaxel in 7%; prior androgen receptor pathway inhibitor treatment was abiraterone in 60%, enzalutamide in 31%, and both in 9%. The primary endpoint was radiographic progression–free survival at 12 weeks, with a significance threshold of P = .15.

Radiographic Progression–Free Survival

Median follow-up was 18 months (95% confidence interval [CI] = 14–22 months). Radiographic progression–free survival at 12 weeks was 64.7% (95% CI = 47.6%–77.5%) in the darolutamide group vs 52.2% (95% CI = 36.1%–66.1%) in the placebo group (difference = 12.5%, lower bound of one-sided 85% CI = 1.1%, P = .127), thus meeting the criterion for significance.

Median radiographic progression–free survival was 5.5 months vs 4.5 months (hazard ratio [HR] = 0.54, 95% CI = 0.32–0.91, P = .017). Median event-free survival was 5.4 months vs 2.9 months (HR = 0.46, 95% CI = 0.29–0.73, P = .001). Median overall survival was 24 months vs 21.3 months (HR = 0.62, 95% CI = 0.3–1.26, P = .181). Among 29 patients with complete or partial radiologic response to the latest ARPI, hazard ratios were 0.35 (95% CI = 0.14–0.87, P = .019) for radiographic progression–free survival and 0.26 (95% CI = 0.06≠1.19, P = .063) for overall survival.

Time to prostate-specific antigen (PSA) progression was 2.7 months vs 1.9 months (HR = 0.48, 95% CI = 0.30–0.77, P = .001). PSA 50% response rate was 22% vs 4% (P = .014).


  • Darolutamide maintenance improved radiographic progression–free survival at 12 weeks and median radiographic progression–free survival vs placebo.
  • Radiographic progression–free survival at 12 weeks was 64.7% vs 52.2%.

Adverse Events

For the darolutamide vs placebo groups, treatment-related grade 1, 2, and 3 adverse events occurred in 26% vs 22%, 13% vs 15%, and 2% vs 2% of patients, respectively. No treatment-related grade 4 or 5 adverse events occurred. Two deaths unrelated to treatment or disease progression occurred in the placebo group, due to sepsis and intracranial hemorrhage.

The investigators concluded, “SAKK 08/16 met its primary endpoint, showing that switch maintenance with darolutamide after prior taxane chemotherapy and at least one [androgen receptor pathway inhibitor] resulted in a statistically significant but clinically modest radiographic progression–free survival prolongation with good tolerability. The median overall survival with darolutamide maintenance appears promising. Should these findings be confirmed in a larger trial, maintenance treatment could be a novel strategy in managing patients with metastatic castration-resistant prostate cancer, especially those who responded well to prior [androgen receptor pathway inhibitor].”

Dr. Gillessen, of Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by Bayer HealthCare Pharmaceuticals Inc. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.