Darolutamide/ADT Combo Delays Disease Worsening in Some PC, Phase 3 Trial Shows

Darolutamide in combination with androgen deprivation therapy (ADT) delays disease worsening in men with non-metastatic castration-resistant prostate cancer (nmCRPC) and stabilizes their quality of life without increasing the incidence of adverse events, new data from a Phase 3 trial shows.

The findings were presented in an oral presentation titled, “Impact of darolutamide (DARO) on pain and quality of life (QoL) in patients (Pts) with nonmetastatic castrate-resistant prostate cancer (nmCRPC),” at the recent 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

Darolutamide, also known as ODM-201 or BAY-1841788, is an investigational prostate cancer therapy being developed by Bayer and Orion. It is an androgen receptor antagonist that binds to the receptor, interrupting the androgen signaling cascade and preventing cancer cells from receiving growth signals.

The safety and efficacy of darolutamide among patients with nmCRPC is being tested in a multi-center, randomized, double-blind, placebo-controlled, Phase 3 trial (NCT02200614), called ARAMIS. The study enrolled 1,509 patients who were randomly assigned to receive either darolutamide or a placebo, twice a day, while they continued treatment with ADT.

The first results from the trial were recently presented at the 2019 Genitourinary Cancers Symposium in San Francisco, and published in the New England Journal of Medicine in a study titled, “Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer.”

According to ARAMIS topline data, darolutamide prolonged the time patients lived without cancer spreading to other tissues and organs from 18.4 months to 40.4 months, which corresponds to a reduction of 59% in the risk of cancer spread or death.

In addition, darolutamide extended the time patients lived without their disease worsening from 14.8 months to 36.8 months, which corresponds to a reduction of 62% in the risk of disease progression or death.

In general, adverse events were similar among patients receiving darolutamide or a placebo. Treatment with darolutamide did not increase the risk of serious adverse events, including seizures, falls, bone fractures, cognitive impairment, or high blood pressure, nor the number of patients who discontinued treatment.

Bayer and Orion have now presented updated data from ARAMIS showing that:

• Darolutamide prolonged the time patients lived without their pain worsening from 25.4 months to 40.3 months;
• Patients receiving darolutamide had a stable quality of life, which was maintained even beyond the end of the treatment period, with scores similar to placebo plus ADT;
• Darolutamide delayed the onset of urinary symptoms from 11.5 months to 18.4 months, and bowel symptoms from 4.8 to 25.8 months;
• The incidence of treatment-emergent adverse events was similar among patients treated with darolutamide or a placebo, and included fatigue (11.3% vs. 11.1%), high blood pressure (4.7% vs. 5.1%), falls (3.0% vs. 4.6%), cognitive disorders (0.3% vs. 0.2%) and memory loss (0.4% vs. 1.2%).

“The results from the ARAMIS trial published recently in the New England Journal of Medicine showed that darolutamide is highly effective in the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and that darolutamide has an excellent safety profile that resembles that of placebo,” Christer Nordstedt, MD, PhD, senior vice president of Research and Development at Orion, said in a press release.

“The new analyses from the ARAMIS trial show that patients treated with darolutamide maintain their quality of life while on darolutamide treatment, which is very good news for the patients. These highly important results encourage us further to bring this treatment to nmCRPC patients as soon as possible,” Nordstedt said.

Karim Fizazi, MD, PhD, professor of medicine at France’s Institut Gustave Roussy, University of Paris Sud, said: “At this stage of prostate cancer, when men typically feel well and generally do not have symptoms, it is important that we have potential treatment options that will prevent the spread of prostate cancer for as long as possible, while limiting burdensome side effects of therapy, which allows patients to continue their day-to-day lives.

“These new data demonstrate darolutamide’s ability to maintain patients’ quality of life while receiving treatment. When you add these findings to previously reported data, the product has the potential to become an important treatment option for men with nmCRPC.”

Based on the trial’s findings, the U.S. Food and Drug Administration (FDA) has granted Priority Review to the New Drug Application (NDA) seeking the approval of darolutamide. Bayer has also submitted applications seeking the approval of darolutamide in Europe, Japan, and other countries.