Data from the Phase III ARANOTE trial, presented at the 2024 European Society for Medical Oncology (ESMO) Congress and published in The Journal of Clinical Oncology, reveal that NUBEQA® (darolutamide) combined with androgen deprivation therapy (ADT) significantly improves radiological progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). The study demonstrated a 46% reduction in the risk of disease progression or death compared to placebo plus ADT (HR 0.54; 95% CI 0.41-0.71; P<0.0001). These findings support the expanded use of darolutamide in mHSPC, regardless of chemotherapy use.
The ARANOTE trial, a randomized, double-blind, placebo-controlled study, involved 669 patients with mHSPC who were randomized in a 2:1 ratio to receive either 600 mg of NUBEQA (n=446) or placebo (n=223) twice daily, in addition to ADT. The primary endpoint was rPFS, while secondary endpoints included overall survival (OS), time to castration-resistant prostate cancer (CRPC), and safety assessments.
Key Findings from the ARANOTE Trial
The results of the rPFS analysis were consistent across various subgroups, showing a 40% risk reduction (HR 0.60, 95% CI: 0.44-0.80) in patients with high-volume mHSPC and a 70% risk reduction (HR 0.30, 95% CI: 0.15-0.60) in those with low-volume disease. Although immature, overall survival data showed a trend towards improvement with an HR of 0.81 (95% CI 0.59-1.12) compared to placebo plus ADT. The ARANOTE data also indicated clinical benefits in delaying the time to CRPC (HR 0.40; 95% CI, 0.32-0.51), time to PSA progression (HR 0.31; 95% CI 0.23-0.41), and time to pain progression (HR 0.72; 95% CI 0.54-0.96).
Safety and Tolerability
The safety profile of NUBEQA was consistent with previous trials. The rates of serious adverse events were similar between the treatment arms (23.6% for NUBEQA plus ADT vs. 23.5% for placebo plus ADT). Discontinuation due to treatment-emergent adverse events (TEAEs) was 6.1% in the NUBEQA plus ADT group compared to 9% in the placebo plus ADT group. The incidence of fatigue was also lower with NUBEQA plus ADT (5.6%) than with placebo plus ADT (8.1%).
Expert Commentary
Fred Saad, Professor and Chairman of Surgery and Director of Genitourinary Oncology at the University of Montreal Hospital Center (CHUM), and Principal Investigator of the ARANOTE trial, stated, “Each diagnosis of metastatic hormone-sensitive prostate cancer is unique, shaped by factors such as age, comorbidities and patient preferences. Each patient therefore requires a tailored treatment approach that thoughtfully addresses these key considerations. With the positive results from ARANOTE, in addition to the ARASENS data, darolutamide has now demonstrated efficacy and safety data both with and without chemotherapy in mHSPC.”
Neal Shore, M.D., FACS, Medical Director, Carolina Urologic Research Center, added, “The positive outcomes from the ARANOTE trial provide physicians with additional data that could broaden the use of NUBEQA as a treatment option for more patients with metastatic hormone-sensitive prostate cancer, which accounts for approximately 10% of prostate cancer diagnoses in the United States. These data demonstrate the potential of this therapy to provide significant benefits to patients with mHSPC, regardless of chemotherapy use.”
About NUBEQA (darolutamide)
NUBEQA® (darolutamide) is an androgen receptor inhibitor (ARi) that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. It is currently indicated in the U.S. for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and mHSPC in combination with docetaxel.
Future Implications
Bayer plans to submit the ARANOTE trial data to the U.S. Food and Drug Administration (FDA) to support the expanded use of NUBEQA in patients with mHSPC. These findings, along with data from the ARASENS trial, could solidify darolutamide as a key treatment option for men with mHSPC.
