Bayer's NUBEQA (darolutamide) plus androgen deprivation therapy (ADT) has demonstrated a significant breakthrough in treating metastatic hormone-sensitive prostate cancer (mHSPC). The Phase III ARANOTE trial, presented at ESMO 2024, revealed a 46% reduction in the risk of progression or death compared to placebo plus ADT (HR 0.54; 95% CI 0.41-0.71; P<0.0001). This improvement in radiological progression-free survival (rPFS) marks a significant advancement in mHSPC treatment, potentially broadening NUBEQA's use in this patient population.
ARANOTE Trial Results
The ARANOTE trial randomized 669 patients with mHSPC in a 2:1 ratio to receive either 600 mg of NUBEQA twice daily or a placebo, both in addition to ADT. The primary endpoint was radiological progression-free survival (rPFS). The results showed a statistically significant and clinically meaningful improvement in rPFS for the NUBEQA plus ADT arm. According to Fred Saad, Principal Investigator of the ARANOTE trial, these results, combined with data from the ARASENS trial, demonstrate darolutamide's efficacy and safety both with and without chemotherapy in mHSPC.
The safety profile of NUBEQA remained consistent with previous studies. Serious adverse events occurred at similar rates in both the NUBEQA plus ADT group (23.6%) and the placebo plus ADT group (23.5%). Treatment-emergent adverse events leading to discontinuation were slightly lower in the NUBEQA group (6.1%) compared to the placebo group (9%). No new safety signals were identified, reinforcing the drug's established safety profile.
NUBEQA's Role in mHSPC Treatment
Metastatic hormone-sensitive prostate cancer (mHSPC) represents approximately 10% of all prostate cancer diagnoses in the U.S. It is characterized by cancer that has spread beyond the prostate but remains responsive to hormone therapy. Standard treatment involves androgen deprivation therapy (ADT) often combined with other therapies to improve outcomes. NUBEQA (darolutamide) is already approved for non-metastatic castration-resistant prostate cancer and, in combination with docetaxel, for mHSPC. The ARANOTE and ARASENS trials are aimed at further defining its efficacy, with or without chemotherapy.
Future Expansion and Regulatory Plans
Experts suggest that the ARANOTE findings could expand NUBEQA's use in treating mHSPC. Neal Shore, M.D., Medical Director of Carolina Urologic Research Center, noted that the positive outcomes provide physicians with additional data supporting NUBEQA as a treatment option for more patients with mHSPC, regardless of whether they undergo chemotherapy. Bayer intends to submit the ARANOTE data to the U.S. Food and Drug Administration (FDA) to broaden NUBEQA’s label for mHSPC. Christian Rommel, Ph.D., Head of Research and Development at Bayer’s Pharmaceuticals Division, emphasized the goal of expanding NUBEQA's availability to as many patients as possible. The ARANOTE trial results were presented at the 2024 European Society for Medical Oncology (ESMO) Congress and published in The Journal of Clinical Oncology.
Prostate Cancer: Incidence and Current Treatment Landscape
Prostate cancer is the second most common cancer in men and the fifth leading cause of cancer death worldwide. In 2020, approximately 1.4 million men were diagnosed with prostate cancer globally, including nearly 300,000 cases in the U.S. At diagnosis, most men have localized disease treatable with surgery or radiotherapy. However, about 10% present with mHSPC, requiring hormone therapy such as ADT, androgen receptor inhibitors (ARi) plus ADT, or chemotherapy (docetaxel) plus ADT. Despite these treatments, many men with mHSPC eventually progress to castration-resistant prostate cancer (CRPC), a more challenging condition to treat.
