ESMO 2024 Late-Breaking Data: Phase III ARANOTE Trial Shows NUBEQA® (darolutamide) Significantly Reduced Risk of Radiological Progression or Death in Metastatic Hormone-Sensitive Prostate Cancer

  • In the Phase III ARANOTE trial, NUBEQA® (darolutamide) plus androgen deprivation therapy (ADT) demonstrated an improvement in radiological progression-free survival (rPFS) with a 46% statistically significant reduction in the risk of progression or death (HR 0.54; 95% CI 0.41-0.71; P<0.0001) compared to placebo plus ADT
  • With these results, NUBEQA plus ADT now has demonstrated efficacy data in metastatic hormone-sensitive prostate cancer (mHSPC) both with and without docetaxel in the pivotal Phase III ARANOTE and ARASENS trials
  • Results were consistent with the established safety profile of NUBEQA with no new safety signals observed
  • ARANOTE results have been published simultaneously in The Journal of Clinical Oncology

Reno, Nevada (UroToday.com) -- Results from the investigational pivotal Phase III ARANOTE trial demonstrated that NUBEQA® (darolutamide) plus androgen deprivation therapy (ADT) showed a statistically significant and clinically meaningful improvement in radiological progression-free survival (rPFS) compared to placebo plus ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC). 1 The results were presented today as a late-breaking oral presentation at the 2024 European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain, and published simultaneously in The Journal of Clinical Oncology.


The results were consistent with the established safety profile of NUBEQA, with no new safety signals observed. Rates of serious adverse events were similar between the treatment arms (23.6% for NUBEQA plus ADT compared to 23.5% for placebo plus ADT), while discontinuation due to treatment-emergent adverse events (TEAEs) was 6.1% in patients treated with NUBEQA plus ADT compared to 9% in patients receiving placebo plus ADT. 1

NUBEQA is indicated in the U.S. for the treatment of adult patients with mHSPC in combination with docetaxel and for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC). 2

The randomized, double-blind, placebo-controlled Phase III ARANOTE trial was designed to assess the efficacy and safety of NUBEQA plus ADT in patients with mHSPC. A total of 669 patients were randomized 2:1 to receive either 600 mg of NUBEQA (N=446) or placebo (N=223) twice daily in addition to ADT. 1

“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,” said 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. “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.”

“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,” said Neal Shore, M.D., FACS, Medical Director, Carolina Urologic Research Center. “These data demonstrate the potential of this therapy to provide significant benefits to patients with mHSPC, regardless of chemotherapy use.”

“The ARANOTE trial was designed to investigate NUBEQA plus ADT compared to placebo plus ADT to provide an additional treatment option for patients with metastatic hormone-sensitive prostate cancer,” said Christian Rommel, Ph.D., Head of Research and Development at Bayer’s Pharmaceuticals Division. “Supported by our robust clinical development program, our goal is to expand the option of NUBEQA to as many patients as possible.”

Bayer plans to submit the data from the ARANOTE trial to the U.S. Food and Drug Administration (FDA) to support the expanded use of NUBEQA in patients with mHSPC.

Detailed Results from ARANOTE 1

Results of the rPFS analysis were consistent across prespecified subgroups, including 40% risk reduction (HR 0.60, 95% CI: 0.44-0.80) in patients with high-volume mHSPC and 70% risk reduction (HR 0.30, 95% CI: 0.15-0.60) in patients with low-volume disease. An analysis of immature overall survival data (OS), which measures the time from treatment until death from any cause, showed an HR of 0.81 (95% CI 0.59-1.12) versus placebo plus ADT. The ARANOTE data also suggested clinical benefits across all other secondary endpoints, including delaying the time to castration-resistant prostate cancer (CRPC) (HR 0.40; 95% CI, 0.32-0.51), time to PSA progression (HR 0.31; 95% CI 0.23-0.41), time to pain progression (HR 0.72; 95% CI 0.54-0.96), and time to initiation of subsequent systemic therapy (HR 0.40; 95% CI 0.29-0.56), compared to placebo plus ADT, though not assessed for statistical significance.

Incidence rates for adverse events Grade 3 or higher were similar between the two groups (35.5% and 35.7%, respectively). The incidence of fatigue was lower with NUBEQA plus ADT than with placebo plus ADT (5.6% and 8.1%, respectively).

Source: Bayer. (2024). ESMO 2024 Late-Breaking Data: Phase III ARANOTE Trial Shows NUBEQA® (darolutamide) Significantly Reduced Risk of Radiological Progression or Death in Metastatic Hormone-Sensitive Prostate Cancer [Press release]. https://bayer2019tf.q4web.com/news/news-details/2024/ESMO-2024-Late-Breaking-Data-Phase-III-ARANOTE-Trial-Shows-NUBEQA-darolutamide-Significantly-Reduced-Risk-of-Radiological-Progression-or-Death-in-Metastatic-Hormone-Sensitive-Prostate-Cancer/default.aspx.

Related Content:

ARANOTE Study: Transforming Metastatic Hormone Sensitive Prostate Cancer Treatment - Fred Saad 

ESMO 2024: Efficacy and Safety of Darolutamide plus ADT in Patients with mHSPC from the Phase 3 ARANOTE Trial