Bayer's Nubeqa (Darolutamide) in Phase 3 ARAMIS Trial Shows Delay in First Invasive Prostate Cancer-Related Surgery for nmCRPC Patients

September 15, 2021 /BioonBIOON/ --Bayer(Bayer) recently announced at the 116th Annual Meeting of the American Urological Association (AUA) in late 2021Novel Prostate Cancer Drug Nubeqa (darolutamide)Assessment of a Post Hoc Analysis of the Phase 3 ARAMIS Trial: Data Reinforce the Established Clinical Profile of Nubeqa in Patients with Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC)

Nubeqa, co-developed by Bayer and the Finnish pharmaceutical company Orion, has been approved in the United States, the European Union, and numerous other countries for the treatment of male patients with nmCRPC. This drug is aAn oral nonsteroidal androgen receptor (AR) inhibitor featuring a unique chemical structure that binds to the receptor with high affinity, exhibiting potent antagonistic activity, thereby inhibiting receptor function and prostate cancer cell growth. Unlike other existing nmCRPC treatments, Nubeqa does not cross the blood-brain barrier, resulting in fewer potential drug interactions and central nervous system (CNS) adverse effects (such as seizures, falls, and cognitive impairment).

The analysis presented at the meeting found that,Compared with androgen deprivation therapy (ADT), the Nubeqa + ADT regimen prolonged the time to first prostate cancer-related invasive procedure., this was an exploratory endpoint (4.7% vs. 9.6%; HR = 0.416; 95% CI: 0.279–0.620).

In a post hoc assessment:Compared with ADT, Nubeqa + ADT in EuropeTumorfurther delayed the time to deterioration in quality of life (QoL) in 2 of the 6 subscales of the EORTC Quality of Life Questionnaire (EORTC QLQ-PR25)：Urinary symptoms(25.8 months vs 14.8 months; HR=0.64; 95% CI: 0.54-0.76) and# Intestinal Symptoms(18.4 months vs 11.5 months; HR = 0.78; 95% CI: 0.66-0.92).

In the primary analysis of the Phase 3 ARAMIS trial, serious adverse reactions occurring in ≥1% of patients treated with Nubeqa included: urinary retention, pneumonia, and hematuria.

Neal Shore, Medical Director of the CPI Urologic Analysis Center in Carolina, USA, stated: “Local signs and symptoms of the prostate and surrounding tissues are highly detrimental to patients' quality of life. In initial nmCRPC treatment discussions between patients and physicians, the incidence of symptoms and the need for invasive procedures are critical. Results regarding quality of life and invasive procedures reinforce the value of Nubeqa in nmCRPC.”

ARAMIS was a randomized, multicenter, double-blind, placebo-controlled phase III trial that enrolled 1,509 male patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who were receiving androgen deprivation therapy (ADT) and were at high risk of developing metastatic disease. The study evaluated the efficacy and safety of oral Nubeqa versus placebo. In the study, patients were randomized in a 2:1 ratio to receive oral Nubeqa 600 mg twice daily or placebo, concomitantly with ADT. Patients with a history of seizures were permitted to participate in the treatment.

Primary efficacy endpoint data showed:Compared with the placebo + ADT regimen (n=554), the Nubeqa + ADT regimen (n=955) significantly prolonged metastasis-free survival (median MFS: 40.4 months vs 18.4 months, p < 0.0001) and significantly reduced the risk of metastasis or death by 59%.。

Additionally, compared with the placebo + ADT regimen, the Nubeqa + ADT regimen significantly prolonged overall survival (OS) and significantly delayed the time to onset of cancer-related symptoms, while minimizing toxicity. The specific data are as follows:Compared with placebo + ADT, the Nubeqa + ADT regimen significantly reduced the risk of death by 31% (HR=0.69; 95% CI: 0.53–0.88; p=0.003), while significantly delaying the time to pain progression (HR=0.65; 95% CI: 0.53–0.79; p<0.0001), time to first cytotoxic chemotherapy (HR=0.58; 95% CI: 0.44–0.76; p<0.0001), and time to first symptomatic skeletal event (SSE), with all these secondary endpoints demonstrating statistically significant improvements.

Notably, a statistically significant OS benefit was also observed, despite more than half (55%, 307 of 554 patients) in the placebo + ADT arm having switched to Nubeqa (31%, 170 patients) or another life-prolonging therapy prior to the final analysis cutoff date (November 15, 2019).

With a median extended follow-up of 29 months in the overall study population, Nubeqa continued to demonstrate a favorable safety profile. Compared with earlier analyses, due toAdverse ReactionsTreatment discontinuation due to (AE) remained unchanged, occurring in 9% of patients in both groups. In addition,The analysis also confirmed that Nubeqa in combination with ADT has minimal impact on the central nervous system (CNS), with a low risk of psychiatric and cognitive disorders.The low blood-brain barrier permeability of Nubeqa, observed in preclinical studies and healthy volunteers, can explain this phenomenon.

Globally, prostate cancer is the second most common malignancy among men.`Tumor`and the fifth leading cause of cancer death, primarily affecting men over the age of 50, with the risk increasing with age. Castration-resistant prostate cancer (CRPC) refers to prostate cancer that continues to progress despite androgen deprivation therapy (ADT) reducing serum testosterone to very low levels. Approximately one-third of patients with non-metastatic CRPC (nmCRPC) develop metastases within two years; therefore, in this clinical setting, the primary goal of treatment is to delay metastatic spread and disease progression while minimizing treatment-related side effects.

Since men with nmCRPC are typically asymptomatic and lead active lives, it is crucial to have treatment options that can delay cancer progression while minimizing treatment side effects, thereby enabling them to maintain their lifestyle with minimal disruption.

In addition to nmCRPC, Bayer and Orion Corporation are also advancing another Phase III clinical trial, ARASENS, to evaluate the efficacy and safety of darolutamide for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). (Bioon.com)

Original Source:NUBEQA® (darolutamide) Impact on Local Symptoms Evaluated in Men with Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC)