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Darolutamide (Nubeqa) was linked with a decrease in locally invasive procedures, as well as local urinary and bowel symptoms, in patients with nonmetastatic (nm) castration-resistant prostate cancer (CRPC), according to analysis of the ARAMIS trial.

The drug, compared with placebo, was also associated with a delayed deterioration in patient quality of life (QoL) related to urinary and bowel symptoms, reported Neal Shore, MD, Carolina Urologic Research Center, Myrtle Beach in South Carolina, at the American Urological Association virtual meeting.

"These findings demonstrate that [darolutamide] had a positive effect on local disease recurrence and symptom control in non-metastatic CRPC," Shore said.

"Patient reported quality of life is one of the most important aspects of clinical decision making, both for physicians and patients," noted Alicia K. Morgans, MD, MPH, of Dana-Farber Cancer Institute in Boston, who was not involved in the study.

"It is great to see this deeper dive into quality of life outcomes in ARAMIS as they provide a clearer view of what patients can expect if treated with darolutamide for nmCRPC," she told 名媛直播.

Darolutamide is an androgen receptor inhibitor (ARi) that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. Based on results from , the the agent for the treatment of nmMCRPC in 2019, with overall survival, and secondary outcome, data in January 2021.

In the trial, 1,509 men with nmCRPC were randomized 2:1 to receive either darolutamide or placebo. Darolutamide was shown to significantly increase metastasis-free survival in these patients, as well as overall survival, compared with placebo.

"Urinary and bowel problems frequently occur with progression of localized prostate cancer and can interfere with patients' quality of life," Shore said. "Thus, it is important for treatment of nonmetastatic CRPC patients to not only delay metastasis and prolong survival, but also control associated symptoms and preserve quality of life."

Shore and his colleagues evaluated the effectiveness of darolutamide on three aspects of local symptom control in ARAMIS patients:

• Incidence and time to first prostate cancer-related locally invasive procedures.
• Time to deterioration in QoL for urinary and bowel symptoms, as measured by the questionnaire prostate cancer module, and the (PCS).
• Incidence of urinary and bowel adverse events (AEs) between treatment groups, and the correlation of AEs with PSA decline from baseline to 16 weeks in the darolutamide arm.

Shore and colleagues found that fewer patients receiving darolutamide (4.7%) underwent locally invasive procedures than patients receiving placebo (9.6%), and that darolutamide was also associated with significantly prolonged time to first procedure compared to placebo (hazard ratio 0.42, 95% CI 0.28-0.62).

As measured with the EORTC-QLQ-PR25 subscales and compared with placebo, darolutamide significantly delayed the time to deterioration in QoL for total urinary symptoms (25.8 vs 14.8 months, HR 0.64, 95% CI 0.54-0.76) and for each of the separate urinary symptom questions, as well as delayed the time deterioration for total bowel symptoms (18.4 vs 11.5 months, HR 0.78, 95% CI 0.66-0.92), along with each of the bowel symptom questions.

On the FACT-P PCS, darolutamide delayed the time to deterioration for total urinary symptoms (11.1 vs 7.9 months, HR 0.80, 95% CI 0.70-0.91) and for each of the separate urinary symptom questions. However, time to deterioration in trouble moving bowels was not significantly impacted by treatment.

There was little difference between the darolutamide and placebo groups in the incidence of AEs for urinary tract infection (5.3% vs 5.6%), abnormally frequent urination (4.4% vs 3.2%), and hematuria (4.5% vs 5.4%). However, the incidence of AEs was lower for darolutamide versus placebo for urinary retention (3.8% vs 7.4%) and dysuria (2.6% vs 5.2%).

Among darolutamide patients, the greater the PSA response, the lower the incidence of urinary retention and dysuria. For patients with >90% PSA response the incidence of urinary retention and dysuria was 2.2% and 0.5%, respectively, compared with 5.1% for both of these AEs in patients with <50% PSA response.

"No increase in urinary- and bowel-related adverse events compared with placebo confirms the favorable safety profile of darolutamide," Shore observed.

"Not only can these relatively asymptomatic patients expect to largely maintain quality of life, some may even have improvements in urinary and bowel complaints, which are some of the most common issues facing this population," Morgan pointed out. "Early treatment of nmCRPC remains of high importance, not just to prolong metastasis free and overall survival, but to maintain, and possibly improve, life for these men."

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