Nubeqa Improves 3-Year Survival in Nonmetastatic Prostate Cancer

Trial results demonstrated that Nubeqa (darolutamide), an androgen-receptor inhibitor, significantly increased overall survival at three years compared with placebo in men with nonmetastatic, castration-resistant prostate cancer.

This phase 3 trial, which was published in The New England Journal of Medicine, determined that the rate of side effects was similar in the Nubeqa and placebo groups.

“Men with prostate cancer and a rising PSA while on conventional hormonal therapy (androgen deprivation therapy or ADT) and no detectable metastases were in a situation of unmet need with no available option to treat their cancer until recently,” said Dr. Karim Fizazi, professor of medical oncology and head of service at Institut Gustave Roussy at the University of Paris-Saclay in France, in an interview with CURE®. “We show that not only (Nubeqa) reduces the risk of developing metastases by about 60%, but it can also reduce the risk of death by more than 30%.”

Nonmetastatic, castration-resistant prostate cancer is often diagnosed with increasing prostate-specific antigen levels and no detectable metastases (or cancer spread to other areas of the body). This can increase a man’s risk of developing metastatic disease and symptoms related to cancer if they were originally asymptomatic. The therapeutic goals for patients with nonmetastatic, castration-resistant prostate cancer include delaying cancer-related symptoms, prolonging survival and minimizing side effects from treatment.

In this trial, researchers compared Nubeqa with placebo in 1,509 men with castration-resistant prostate cancer who were treated with androgen-deprivation therapy, or hormone therapy often used to treat prostate cancer. These men were randomly assigned either 600 mg of Nubeqa twice per day with food (955 men) or placebo (554 men), both of which were administered until discontinuation from side effects, disease progression or initiation of another anticancer therapy. During this portion of the trial, men who were originally assigned placebo could join the treatment group if their doctor determined it was necessary.

Patients were followed up every 16 weeks until the end of the trial for a median of 29 months. During this time, researchers monitored for secondary end points, including time to pain progression (including an increase in pain score or prescribing opioid treatment), overall survival (OS), time to first symptomatic skeletal event (ie, bone fracture, a tumor-related orthopedic surgery, spinal cord compression or external-beam radiation for skeletal symptoms) and the time to first use of cytotoxic chemotherapy (drugs to kill cancer cells).

During the trial, 170 men assigned placebo crossed over to the other group to initiate treatment with Nubeqa.

At three years, OS was 83% for men assigned Nubeqa versus 77% of those assigned placebo. Nubeqa lowered the risk of death by 31% compared with placebo. In addition, men assigned Nubeqa significantly benefitted with regards to time to first use of cytotoxic chemotherapy and the time to first symptomatic skeletal event.

Both groups had similar rates of side effects, with 85.7% of men in the Nubeqa group and 79.2% of those in the placebo group. Side effects occurred in 70% of men who crossed over from placebo to Nubeqa. Researchers did not observe new safety signals compared with the trial’s initial analysis.

“This data is clearly a game changer for this population of men, and guidelines have been updated accordingly,” said Fizazi. “On top of this, the safety profile of (Nubeqa) is remarkable, with almost no detectable effect over a placebo, which is quite unique in this situation.”

Although the trial is promising regarding the treatment’s benefit, there are some questions that remain unanswered. “A limitation of the trial is the small size of some subgroups, and hence, the low numbers of events in these subgroups and the low numbers of patients of particular races or ethnic groups (eg, only 52 patients of African descent); therefore, no conclusions can be drawn about efficacy in these specific group of patients,” the study authors wrote.

Fizazi said that further research should focus on integrating imaging to determine how to manage disease in these men. He said, “It is likely that next-generation imaging will soon be also integrated in the management of these men. This technology will more and more allow early detection of micro-metastases and, thus, their local treatment on top of (Nubeqa). This should be the subject of the coming generation of clinical trials.”

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