FDA Adds New Data to Label for Darolutamide in nmCRPC

In response to the drug’s developer, the FDA added overall survival and other end point data to the label of darolutamide for its indication for treating patients with nonmetastatic castration-resistant prostate cancer who are receiving standard androgen-deprivation therapy.

Overall survival (OS) results and other secondary outcome data were added to the prescribing information for the androgen receptor inhibitor darolutamide (Nubeqa) as a result of the FDA approving a supplemental new drug application (sNDA) from Bayer, the manufacturer of the agent.1

The data that are now included on the label are from the phase 3 ARAMIS trial (NCT02200614) whose results were published in September in The New England Journal of Medicine.2 Data from this trial resulted in the FDA approving darolutamide in 2019 as therapy for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) based on the trial meeting its primary end point of metastasis-free survival.3

“A key goal of cancer treatment is to ensure that patients can live longer while minimizing side effects,” Scott Z. Fields, MD, senior vice president and head of Oncology Development at Bayer’s Pharmaceutical Division, said in a press release. “Nubeqa has a proven efficacy and safety profile in men with nmCRPC and delayed the effects of disease progression in men who are otherwise generally asymptomatic. This update also gives physicians added certainty that Nubeqa should be prescribed to appropriate patients at nmCRPC diagnosis to help ensure optimal outcomes for these men.”

In conjunction with androgen-deprivation therapy (ADT), darolutamide reduced the risk of death by 31% versus placebo (HR, 0.69; 95% CI, 0.53-0.88; P = .003) in patients with nmCRPC. At 3 years, the rates of OS were 83% with darolutamide versus 77% for placebo. The trial investigators noted that the effect of darolutamide on OS was statistically significant despite a high rate of patients in the placebo arm (55%) crossing over to the experimental-therapy arm.

The trial also demonstrated that darolutamide delayed time to pain progression—defined as worsening from baseline on the Brief Pain Inventory-Short Form of 2 points or more or initiation of opioids—versus placebo in this group of patients, at medians of 40.3 months versus 25.4 months, respectively (HR, 0.65; 95% CI, 0.53-0.79; P <.0001). Additionally, time to initiation of cytotoxic therapy was reduced with darolutamide, with 83% of patients in this arm having not yet received chemotherapy versus 75% in the placebo arm (HR, 0.58; 95% CI, 0.44-0.76; P <.0001). These results are now included on the label.

No changes were made to the safety data on the label, indicating that no new safety signals were determined at the final analysis. The rate of treatment discontinuation in both the darolutamide and placebo groups remained unchanged from the primary analysis (8.9% vs 8.7%, respectively).

Additional drug interactions were added to the label. Darolutamide inhibits OATP1B1 and OATP1B3 transporters, resulting in increased plasma concentrations with concomitant use that could results in related toxicities that should be monitored for.

The double-blind, placebo-controlled trial randomized 1509 patients in a 2:1 fashion to either the darolutamide (n = 955) or placebo (n = 554) arms while simultaneously receiving ADT. Since the primary end point of the trial was previously met, the trial was unblinded allowing patients in the placebo group to crossover to receive open-label darolutamide therapy.


1. U.S. FDA approves addition of overall survival and other secondary endpoint data to Nubeqa (darolutamide) prescribing information. News release. Published January 8, 2021. Accessed January 8, 2021. https://bayer2019tf.q4web.com/news/news-details/2021/U.S.-FDA-Approves-Addition-of-Overall-Survival-and-Other-Secondary-Endpoint-Data-to-NUBEQA-darolutamide-Prescribing-Information/default.aspx

2. Fizazi K, Shore N, Tammela TL, et al; ARAMIS Investigators. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med. 2020;383(11):1040-1049. doi: 10.1056/NEJMoa2001342

3. FDA approves darolutamide for non-metastatic castration-resistant prostate cancer. FDA. July 30, 2020. Accessed January 8, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-non-metastatic-castration-resistant-prostate-cancer