FDA Updates Prescribing Information for Darolutamide in nmCRPC

The FDA has updated the Prescribing Information for the approved agent darolutamide (Nubeqa) to include improvement in overall survival (OS) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC), as well as other secondary end point data, from the phase 3 ARAMIS clinical trial (NCT02200614), announced Bayer, in a press release.

The decision to update the Prescribing Information was based on results presented at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the New England Journal of Medicine. The results showed that darolutamide reduced the risk of death by 31% in men with nmCRPC (HR, 0.69; 95% CI 0.53-0.88; P =.003). The OS improvement was deemed statistically significant even though 170 out of 955 in the androgen deprivation therapy (ADT) arm crossed over to the darolutamide arm. It was noted that, overall, 55% of the ADT arm crossed over to the darolutamide arm prior to the secondary end point analysis.

In addition to OS, the updated Prescribing Information for darolutamide as treatment of nmCRPC mentions delaying time to pain progression (HR, 0.65; 95% CI, 0.53-0.79; P <.0001), as well as delaying time to initiation of cytotoxic chemotherapy (HR, 0.58, 95% CI, 0.44-0.76; P <.0001).

Time to pain progression in the ARAMIS was defined as at least a 2-point worsening from baseline of the pain score according to the Brief Pain Inventory-Short Form or by the initiation of opioids.

No new safety signals were observed during the secondary end point analysis and, therefore, safety-related Prescribing Information was not updated.

"A key goal of cancer treatment is to ensure that patients can live longer while minimizing side effects," said Scott Z. Fields, MD, senior vice president and Head of Oncology Development at Bayer's Pharmaceutical Division, in a statement. “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.”

As previously reported by Targeted Oncology, results from the primary analysis of the ARAMIS trial showed that darolutamide improved metastasis-free survival (MFS). The median MFS was 40.4 months with darolutamide versus 18.4 months with placebo, which led to a 59% reduction in the risk of metastasis or death (HR, 0.41; 95% CI, 0.34-0.50; P <.0001). The safety profile of the agent was also favorable, according to the primary analysis findings.

ARAMIS is a double-blind, placebo-controlled, multicenter, phase study that investigated the efficacy and safety of darolutamide in combination with ADT compared with placebo. The primary end point of the trial was MFS, and key secondary end points were OS, time to pain progression, time to initiation of first cytotoxic chemotherapy, time to the first symptomatic skeletal event, and characterization of the safety and tolerability of the androgen receptor inhibitor.

Overall, 1509 patients with nmCRPC were included and randomized in a 2:1 fashion. Treatment with darolutamide 600 mg was administered twice daily with food.

Eligible patients included those with histologically or cytologically confirmed adenocarcinoma of the prostate, an ECOG performance status of 0 to 1, a prostate-specific antigen doubling time of 10 months or less, and adequate laboratory results.

_References:

_{U.S. FDA Approves addition of overall survival and other secondary endpoint data to Nubeqa® (darolutamide) prescribing information. News release. Bayer, Janauray 8, 2020. Accessed January 8, 2020.}