The following article features coverage from the 2021 Genitourinary Cancers Symposium meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Darolutamide was found to significantly prolong overall survival (OS) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC) despite trial unblinding and patient crossover, according to the final analysis of the phase 3 ARAMIS trial. Data from the evaluation, which was conducted after 254 deaths had occurred, were presented at the 2021 Genitourinary Cancers Symposium.

“These findings indicate that darolutamide is an effective and well-tolerated androgen receptor inhibitor as an early treatment option for patients with nmCRPC,” said Neal D. Shore, MD, who reviewed the results.

In the phase 3 ARAMIS trial (NCT02200614), 1509 patients with nmCRPC were randomly assigned to receive either darolutamide or placebo in addition to androgen deprivation therapy. Results from the primary analysis demonstrated that darolutamide significantly prolonged metastasis-free survival compared with placebo (HR, 0.41; 95% CI, 0.34-0.50; P <.0001).

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The trial was unblinded, permitting crossover from the placebo arm to the darolutamide arm. At the time of the final analysis (November 15, 2019), 4 sensitivity analyses were conducted to determine the effect of crossover on OS in the 170 patients (of 554) who crossed over from the placebo arm. The planned analyses were performed using iterative parameter estimation and rank-preserving structural failure time to adjust for crossover.

Crossover from the placebo arm to the darolutamide arm occurred among 30.7% of patients and “had only a small impact on the estimated OS benefit,” Shore said.

Darolutamide significantly prolonged OS compared with placebo (HR, 0.69; 95% CI, 0.53-0.88; P =.003). A similar OS benefit was observed in the iterative parameter estimation (HR, 0.66; 95% CI, 0.51-0.84; P <.001) and rank-preserving structural failure time (HR, 0.68; 95% CI, 0.51-0.90; P =.007) analyses.

Darolutamide’s safety profile continued to be favorable in the final analysis, and the rate of treatment discontinuation at the end of the double-blind period notably remained unchanged from the time of the primary analysis (8.9% with darolutamide and 8.7% with placebo).

“Early treatment with darolutamide in men with nonmetastatic CRPC is associated with significant improvement in OS regardless of patient crossing over from placebo to darolutamide,” Shore concluded.

Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study. This research was supported by Bayer AG and Orion Pharma.

Read more of our coverage of the 2021 Genitourinary Cancers Symposium by visiting the conference page.


Shore ND, Fizazi K, Tammela T, et al. Analysis of the effect of crossover from placebo (PBO) to darolutamide (DARO) on overall survival (OS) benefit in the ARAMIS trial. Presented at: 2021 Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 240.