Reading, UK, 16th September 2024 – Results from the Phase III ARANOTE trial have shown that darolutamide plus androgen deprivation therapy (ADT) significantly reduced the risk of radiological progression or death by 46% compared to placebo plus ADT (HR 0.54; 95% CI 0.41–0.71; P<0.0001), in patients with metastatic hormone-sensitive prostate cancer (mHSPC).1 Consistent benefits in rPFS were observed across prespecified subgroups, including patients with high- and low-volume mHSPC. The incidence of treatment-emergent adverse events (TEAEs) were similar between treatment groups.1 Treatment discontinuations due to TEAEs were lower in patients receiving darolutamide plus ADT compared to placebo plus ADT (6.1% vs 9.0%).1 The results were presented at the 2024 ESMO Congress and simultaneously published in The Journal of Clinical Oncology.
“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 ARANOTE trial. “With the positive results from ARANOTE, in addition to the ARASENS data, darolutamide has now demonstrated strong efficacy and safety both with and without chemotherapy in mHSPC. If regulatory approval is granted, physicians will have greater flexibility to tailor treatment to individual patient needs.”
“The ARANOTE trial was designed to investigate darolutamide with ADT alone to provide an additional option for patients with mHSPC,” said Christian Rommel, Ph.D., Head of Research and Development at Bayer’s Pharmaceuticals Division. “Supported by our robust clinical development programme, darolutamide has the potential to become a foundational therapy in prostate cancer. Our focus is to deliver this potential new treatment option to patients and physicians as quickly as possible.”
"Prostate cancer is not just a diagnosis; it’s a journey that impacts every aspect of a patient’s life. With 1 in 8 men diagnosed in their lifetime in the UK, the emotional, physical, and financial burdens can be overwhelming, affecting not only the individual but their loved ones as well. Research in prostate cancer is therefore vital, as it holds the key to developing effective treatments and improving outcomes. It remains crucial that we continue to advocate for awareness, support and resources that empower patients and their families on this journey,” said Oliver Kemp, CEO, Prostate Cancer Research.
Bayer plans to submit the data from the ARANOTE trial to health authorities globally and in the UK to support the expanded use of darolutamide in patients with mHSPC.
Detailed results from ARANOTE1
Darolutamide plus ADT significantly reduced the risk of radiological progression or death by 46% (HR 0.54; 95% CI 0.41–0.71; P<0.0001), compared with placebo plus ADT. The primary analysis of rPFS was performed after 222 patients had an rPFS event, with a smaller proportion of patients in the darolutamide group (128/446; 28.7%) compared with the placebo group (94/223; 42.2%). Consistent benefits in rPFS were observed across patient subgroups, including high- and low-volume mHSPC with a risk reduction, by 40% and 70% (HR 0.60; 95% CI 0.44-0.80 and HR 0.30; 95% CI 0.15-0.60), respectively. At this interim analysis, data for overall survival were immature; there were 103/446 [23.1%] deaths in the darolutamide plus ADT group and 60/223 [26.9%] deaths in the placebo plus ADT group (HR=0.81, 95% CI 0.59-1.12). The ARANOTE data also suggested numerical benefits across all other secondary endpoints including 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), 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.
Incidences of treatment-emergent adverse events (TEAEs) were similar between treatment groups (most were grade 1 or 2). The most frequently reported AEs (incidence of ≥10%) for darolutamide plus ADT vs placebo plus ADT, were anemia (20.4% and 17.6%, respectively), arthralgia (12.4% and 11.3%, respectively), and urinary tract infections (11.7% and 7.7%, respectively). The incidence of fatigue was lower with darolutamide plus ADT vs placebo plus ADT (5.6% and 8.1%, respectively). Incidence of TEAEs of interest were similar between treatment groups, with a difference of ≥2% for coronary artery disorders (3.6% and 1.4%, respectively), cardiac arrhythmias (8.8% and 6.8%, respectively), and vasodilation/flushing (9.2% and 7.2%, respectively).
ENDS
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Veronica Yao, +44 (0) 7870 485 926
Email: veronica.yao@bayer.com
Notes to Editors
About the ARANOTE Trial
The ARANOTE trial is a randomised, double-blind, placebo-controlled Phase III study designed to assess the efficacy and safety of darolutamide plus ADT in patients with mHSPC. 669 patients were randomised 2:1 to receive either 600mg of darolutamide twice daily or placebo in addition to ADT.4
The primary endpoint of this study is rPFS, measured as time from randomisation to date of first documented radiological progressive disease or death due to any cause, whichever occurs first. Secondary endpoints include overall survival (time to death from any cause), time to first castration-resistant event, time to initiation of subsequent anti-cancer therapy, time to prostate-specific antigen (PSA) progression, PSA undetectable rates, time to pain progression, and safety assessments.4
About darolutamide (Nubeqa®▼)
Darolutamide is an oral androgen receptor inhibitor (ARi) that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells.5
Darolutamide was authorised in March 2020 in the European Union under the brand name NUBEQA® for the treatment of men with non-metastatic castration resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease.6 It was authorised in November 2022 in the UK for the treatment of patients with mHSPC in combination with docetaxel.5 In May 2023, the National Institute for Health and Care Excellence (NICE) issued guidance (TA903) recommending darolutamide plus ADT in combination with docetaxel as a treatment option for patients with mHSPC.7
The Summary of Product Characteristics (SmPC) for darolutamide can be found at:
https://www.medicines.org.uk/emc/product/11324
About Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
There are over 52,000 cases of prostate cancer in the UK each year,8 with over 15,000 new cases of metastatic prostate cancer confirmed each year.9
Metastatic hormone-sensitive prostate cancer (mHSPC) is cancer that has spread beyond the prostate to other parts of the body and still responds to treatment with hormone therapy.10 mHSPC precedes the development of metastatic castration-resistant prostate cancer (mCRPC),11 which no longer responds to treatment with hormone therapy.
Despite treatment, most men with mHSPC will eventually progress to mCRPC,12 a condition with limited survival.
About Prostate Cancer at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The company has the passion and determination to develop new medicines that help improve and extend the lives of people living with cancer. Prostate cancer is the second most commonly diagnosed cancer in men13 and a key area of focus for Bayer. The company’s franchise includes two products on the market (Nubeqa® and Xofigo®▼(radium-223 dichloride)) and several compounds in development. Bayer is focused on addressing the unique needs of patients with prostate cancer, providing treatments that extend their lives throughout the different stages of the disease and allowing them to continue with their everyday activities, so that patients can live longer, better lives.
▼ 'This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See https://yellowcard.mhra.gov.uk/ for how to report side effects.'
About Bayer
Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2023, the Group employed around 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 billion euros. For more information, go to www.bayer.co.uk.
Forward-Looking Statements
This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.co.uk. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.
References
1. Saad F. et al. Darolutamide in Combination With Androgen-Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer From the Phase III ARANOTE Trial. doi/10.1200/JCO September 2024. Available at: https://ascopubs.org/doi/10.1200/JCO-24-01798
2. Smith, RA, et al. Overall survival with darolutamide versus placebo in combination with androgen-deprivation therapy and docetaxel for metastatic hormone-sensitive prostate cancer in the phase 3 ARASENS trial. Oral Abstract session at the ASCO GU Cancers Symposium, 17-19 February 2022, San Francisco, California, USA. Available at: https://meetings.asco.org/abstracts-presentations/205326. Last accessed: September 2024.
3. Smith, RA, et al. Darolutamide and survival in metastatic hormone-sensitive prostate cancer. NEJM 2022 Feb 17, doi:10.1056/NEJMoa2119115.
4. Darolutamide in Addition to ADT Versus ADT in Metastatic Hormone-sensitive Prostate Cancer (ARANOTE). Clinicaltrial.gov. Available at: https://www.clinicaltrials.gov/study/NCT04736199. Last accessed: September 2024.
5. NUBEQA® (darolutamide) 300 mg film-coated tables Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/11324. Last accessed: September 2024.
6. Nubeqa (darolutamide). European Medicines Agency. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/nubeqa#authorisation-details-section. Last accessed: September 2024.
7. TA903. Darolutamide with androgen deprivation therapy and docetaxel for treating hormone-sensitive metastatic prostate cancer. National Institute for Health and Care Excellence. Available at: https://www.nice.org.uk/guidance/ta903. Last accessed: September 2024.
8. Cancer Research UK. Prostate cancer statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/prostate-cancer. Last accessed: September 2024.
9. Prostate Cancer UK. Advanced prostate cancer: your questions answered about the disease affecting Bill Turnbull. Available at: https://prostatecanceruk.org/about-us/news-and-views/2018/10/advanced-disease-blog. Last accessed: September 2024.
10. Cancer.Net. ASCO answers: Prostate Cancer. Available at: https://www.cancer.net/sites/cancer.net/files/asco_answers_guide_prostate.pdf. Last accessed: September 2024.
11. Cattrini, et al. Current Treatment Options for Metastatic Hormone-Sensitive Prostate Cancer. Cancers.2019 11(9), p.1355.
12. Ritch, C. and Cookson, M. Recent trends in the management of advanced prostate cancer. F1000Res. 2018 Sep 21;7:F1000 Faculty Rev-1513.
13. Bray F et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21834. Last accessed: September 2024.