Positive Results from Phase III Investigational Trial Shows NUBEQA® (darolutamide) Plus Androgen Deprivation Therapy (ADT) and Docetaxel Significantly Increases Overall Survival (OS) in Patients with mHSPC

  • NUBEQA plus androgen deprivation therapy (ADT) and docetaxel showed a statistically significant increase in overall survival (OS) with a reduction in the risk of death by 32.5% compared to ADT plus docetaxel (HR=0.68, 95% CI 0.57-0.80; P<0.001) in patients with metastatic hormone-sensitive prostate cancer (mHSPC)1
  • NUBEQA plus ADT and docetaxel also showed a statistically significant benefit across multiple secondary endpoints, including delay in time to castration-resistant prostate cancer (CRPC), time to pain progression, time to first symptomatic skeletal event (SSE), and time to initiation of subsequent systemic antineoplastic therapy1
  • Incidence of treatment-emergent adverse events (TEAEs) was similar for NUBEQA plus ADT and docetaxel and ADT plus docetaxel1
  • First results from the investigational Phase III ARASENS trial selected for oral presentation at the 2022 ASCO GU Cancers Symposium and simultaneously published in The New England Journal of Medicine1 

Abstract: 13

Reno, Nevada (UroToday.com) -- Results from the investigational Phase III ARASENS trial have shown that the use of oral androgen receptor inhibitor (ARi) NUBEQA® (darolutamide) plus androgen deprivation therapy (ADT) and docetaxel significantly increased overall survival (OS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) compared to ADT plus docetaxel. NUBEQA plus ADT and docetaxel significantly reduced the risk of death by 32.5% compared to ADT plus docetaxel (HR=0.68, 95% CI 0.57-0.80; P<0.001). At the data cutoff date for the primary analysis (October 25, 2021), the median treatment duration was longer for NUBEQA plus ADT and docetaxel (41.0 months) versus ADT plus docetaxel (16.7 months).1 NUBEQA is currently indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

These results were presented at the 2022 ASCO GU Cancers Symposium and simultaneously published in The New England Journal of Medicine.1

“Metastatic prostate cancer is a uniformly fatal disease and despite progress in recent years, only 30% of these men will survive beyond five years. ARASENS demonstrated that the addition of NUBEQA, an androgen receptor inhibitor, significantly increased overall survival for patients receiving standard androgen deprivation therapy and docetaxel as initial treatment for metastatic hormone-sensitive prostate cancer. NUBEQA also improved time to castration-resistant prostate cancer and other key secondary endpoints,” said Matthew Smith, M.D., Ph.D., Director of the Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center. “These results are an important step forward for the treatment of patients with metastatic hormone-sensitive prostate cancer.”
“With the ARASENS results in mHSPC adding to the existing Phase III ARAMIS data in nmCRPC, NUBEQA has now shown positive data in two pivotal clinical trials for patients across these key disease stages in prostate cancer,” said Robert LaCaze, Member of the Executive Committee of Bayer’s Pharmaceutical Division and Head of the Oncology SBU at Bayer. “We believe NUBEQA has the potential to become a foundational drug for appropriate prostate cancer patients. We are committed to making this potential new treatment option in mHSPC available to patients and their treating physicians, and therefore are pursuing the fastest possible regulatory timelines.”

ARASENS is the only randomized, double-blind pivotal study prospectively designed to compare the use of a second-generation ARi plus ADT and docetaxel to ADT plus docetaxel (a guideline recommended standard-of-care) in mHSPC.2

Detailed results from ARASENS

The significant improvement in OS was observed despite substantially higher use of subsequent systemic antineoplastic therapies (such as abiraterone, enzalutamide, cabazitaxel, docetaxel, radium-223 dichloride, sipuleucel-T, lutetium-177 PSMA, or apalutamide) among patients receiving ADT plus docetaxel who entered follow-up (75.6%) compared with the group who received NUBEQA plus ADT and docetaxel (56.8%).1

NUBEQA plus ADT and docetaxel demonstrated statistically significant benefits across multiple secondary endpoints compared to ADT plus docetaxel, including delaying the time to castration-resistant prostate cancer (CRPC) (HR=0.36, 95% CI 0.30-0.42; P<0.001), time to pain progression (HR=0.79, 95% CI 0.66-0.95; P=0.01), time to first symptomatic skeletal event (SSE) (HR=0.71, 95% CI 0.54-0.94; P=0.02) and time to initiation of subsequent systemic antineoplastic therapy (HR=0.39, 95% CI 0.33-0.46; P<0.001).1

Treatment-emergent adverse events (TEAEs) were similar between treatment arms. The most common TEAEs (≥10%) were highest during the overlapping docetaxel treatment period for both arms and decreased progressively thereafter. The most frequently reported AEs in the treatment arms (NUBEQA plus ADT and docetaxel versus ADT plus docetaxel) were alopecia (40.5% and 40.6%, respectively), neutropenia (39.3% and 38.8%, respectively), fatigue (33.1% and 32.9%, respectively) and anemia (27.8% and 25.1%, respectively). Grade 3 or 4 AEs reported in 66.1% versus 63.5% of patients were mainly due to neutropenia (33.7% versus 34.2%, respectively). Serious AEs occurred in 44.8% versus 42.3% of patients, and TEAEs leading to treatment discontinuation occurred in 13.5% versus 10.6% of patients.1

AEs of special interest in patients treated with AR pathway inhibitors for prostate cancer such as fatigue falls, fractures, mental impairment, and cardiovascular events were similar between study arms.

References:

  1. Smith M., Hussain M., Saad F. et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022.
  2. ClinicalTrials.gov NCT02799602. ODM-201 in Addition to Standard ADT and Docetaxel in Metastatic Castration Sensitive Prostate Cancer (ARASENS).  https://clinicaltrials.gov/ct2/show/NCT02799602.

Source: "Positive Results From Phase III Investigational Trial Shows NUBEQA® (Darolutamide) Plus Androgen Deprivation Therapy (ADT) And Docetaxel Significantly Increases Overall Survival (OS) In Patients With Mhspc | Biospace". 2022. Biospace.
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