Darolutamide Significantly Delays Time to Decrease in HRQL in nmCRPC

The androgen receptor inhibitor darolutamide (Nubeqa) has been shown to significantly delay the time to locally invasive procedures as well as the time to deterioration in health-related quality of life (HRQOL) measures in patients with castration-resistant non-metastatic prostate cancer (nmCRPC), investigators reported at the 2021 annual meeting of the American Urological Association.¹

For the study, the researchers evaluated the effect of darolutamide on local symptom control. Specifically, they examined the incidence and time to first invasive procedures related to prostate cancer, time to deterioration in health-related quality of life measures, and the incidence of adverse events related to prostate cancer. urinary and bowel therapy and their correlation with lower PSA between baseline and week 16. in patients receiving darolutamide.

The time to deterioration of HRQL measurements was assessed using the Prostate Cancer module of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire and the FACT-P (Functional Assessment of Cancer Therapy-Prostate) subscale for prostate cancer.

When assessing the incidence and time to first locally invasive procedures, “the results of these analyzes showed that fewer patients receiving darolutamide, 4.7%, underwent locally invasive procedures, compared to patients receiving placebo. , 9.6%, ”said first author Neal D. Shore, MD, FACS, director of the Carolina Urologic Research Center in Myrtle Beach, SC. The most common procedures included catheterization, transurethral resection of the prostate, nephrostomy, and surgical excisions and resections.

Darolutamide also significantly prolonged the time to the first locally invasive procedure for prostate cancer compared to placebo (hazard ratio [HR], 0.42; 95% CI 0.28-0.62).

“For the EORTC urinary symptoms subscale, darolutamide significantly delayed the time to deterioration in quality of life for total urinary symptoms and for each individual urinary symptom question compared to placebo,” said Shore.

The 4 issues that most contributed to the time to deterioration of HRQOL with darolutamide were:

• urinate frequently during the day (HR, 0.764; 95% CI: 0.648-0.902)

• urinate frequently at night (RR: 0.664; 95% CI: 0.559-0.790)

• pain when urinating (RR: 0.569; 95% CI: 0.441-0.734)

• urinary problems interfere with daily activities (HR, 0.748; 95% CI, 0.614-0.910).

Darolutamide was also found to significantly delay the time to deterioration of total bowel symptoms compared to placebo (RR: 0.781; 95% CI: 0.664-0.918).

“For each of the 4 items related to intestinal symptoms, darolutamide delayed the time to deterioration compared to placebo with risk ratios ranging from 0.87 to 0.91, but the 95% confidence intervals were wide and exceeded 1, “Shore said.

For the prostate cancer FACT-P subscale, darolutamide significantly delayed the time to deterioration for total urinary symptoms as well as for each of the 3 urinary symptoms questions. However, the time to deterioration of bowel movements was not significantly affected by darolutamide treatment (HR, 1.089; 95% CI, 0.0862-1.376).

In the overall study population, urinary retention occurred in 36 patients (3.8%) in the treatment arm vs. 41 patients (7.4%) in the placebo arm. Dysuria occurred in 25 patients (2.6%) in the treatment arm versus 29 patients (5.2%) in the placebo arm.

“The incidences of other urinary and intestinal adverse events showed minimal differences of 2% or less between treatments,” Shore said.

In addition, in patients treated with darolutamide, a higher prostate specific antigen response was associated with a lower incidence of urinary retention and dysuria.

Specifically, patients receiving darolutamide who had a decrease in PSA of 90% or more between baseline and week 16 had incidences of urinary retention and dysuria of 2.2% and 0.5% respectively, versus 5 , 1% for urinary retention and dysuria in patients with a PSA response of less than 50%.

“In conclusion, darolutamide has been associated with a reduction in locally invasive procedures and a delay in the deterioration of the quality of life of patients with regard to urinary and intestinal symptoms. The absence of an increase in urinary and intestinal adverse events compared to placebo confirms the favorable safety profile of darolutamide. These results demonstrate that darolutamide had a positive effect on local disease recurrence and symptom control in patients with non-metastatic CRPC, ”said Shore.

Reference

1. Shore S, Stenzl A, Pieczonka C, et al. Impact of darolutamide on local symptoms in patients with non-metastatic castration-resistant prostate cancer. Paper presented at the American Urological Association annual meeting in 2021; September 10-13; virtual. Summary PD34-10