Darolutamide shows significant increase in overall survival and decrease in disease progression in men with metastatic hormone-sensitive prostate cancer

Results from the pivotal Phase III ARASENS clinical trial have shown the use of the oral androgen receptor inhibitor (ARi) darolutamide plus ADT and docetaxel significantly reduced the risk of death by 32.5% compared to docetaxel plus ADT (HR=0.68, 95% CI 0.57-0.80; P<0.001) in men with metastatic hormone-sensitive prostate cancer (mHSPC).^1,2 These data were presented at the 2022 ASCO GU Cancers Symposium¹ and simultaneously published in The New England Journal of Medicine.²

In addition, treatment with darolutamide showed consistent improvements in key secondary endpoints, including delaying the time to castration-resistance prostate cancer (CRPC) by 64.3% compared to the placebo arm (HR=0.36, 95% CI 0.30-0.42; P<0.001).^1,2 Darolutamide plus ADT and docetaxel also significantly delayed time to pain progression by 20.8% compared to placebo (HR=0.79, 95% CI 0.66-0.95; P=0.01), time to first symptomatic skeletal event (SSE) by 28.8% (HR=0.71, 95% CI 0.54-0.94; P=0.012) and time to initiation of subsequent systemic antineoplastic therapy by 61.2% (HR=0.39, 95% CI 0.33-0.46; P<0.001).^1,2

“Despite existing effective treatments, many men with metastatic hormone-sensitive prostate cancer (mHSPC) will unfortunately progress to metastatic castration-resistant prostate cancer (mCRPC) within 2-3 years, when treatment options become more limited,” said Professor Alison Birtle, Consultant Clinical Oncologist at Lancashire Teaching Hospitals NHS Foundation Trust, adding: “The exciting results from the ARASENS study show that darolutamide given with two other standard treatments for newly diagnosed metastatic prostate cancer can make men live longer and have a good quality of life. We need more treatments like darolutamide and I hope the novel combination of these three treatments will soon be available on the NHS for men with mHSPC in the UK.”

Dr Matthew Hobbs, Director of Research at Prostate Cancer UK said: “Treatment for advanced prostate cancer that is still responding to hormone therapy has improved rapidly in the past six years. The results of the ARASENS study show that adding darolutamide to androgen deprivation therapy and docetaxel could give men with advanced prostate cancer even longer life expectancy.

“The definitive results presented today also point the way towards our next research priorities. We must now learn exactly which men respond best to this triplet therapy approach so that we can maximise the benefit of this and other new treatment combinations.”

AEs were similar between treatment arms.^1,2 The most common AEs (≥10%) were highest during the overlapping docetaxel treatment period for both arms and decreased progressively thereafter.^1,2 The most frequently reported AEs in the treatment arms (darolutamide plus ADT and with docetaxel versus docetaxel plus ADT) were alopecia (40.5% and 40.6%, respectively), neutropenia (39.3% and 38.8%, respectively), fatigue (33.1% and 32.9%, respectively) and anaemia (27.8% and 25.1%, respectively).¹ 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), which is a well-known effect of docetaxel treatment.^1,2Serious AEs occurred in 44.8% versus 42.3% of patients, and AEs leading to treatment discontinuation occurred in 13.5% versus 10.6% of patients.^1,2

“Added to the existing Phase III ARAMIS data in non-metastatic castration-resistant prostate cancer (nmCRPC), the data from ARASENS demonstrate darolutamide’s significant efficacy and promising safety profile for patients across several key disease stages in prostate cancer,” said Mike Metcalfe, UK Medical Director at Bayer. “We believe darolutamide 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 physicians as soon as possible, reinforcing our dedication to treating patients across the wide spectrum of prostate cancer”.

ARASENS (NCT02799602) is the only randomised, prospectively designed, double-blind pivotal study comparing the use of a second-generation ARi, darolutamide, plus ADT and docetaxel to a guideline recommended standard-of-care (docetaxel plus ADT) in mHSPC.³

Darolutamide was developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company. The compound is also being investigated in further studies across various stages of prostate cancer, including another Phase III trial in mHSPC (ARANOTE),⁴ as well as a Phase III trial evaluating darolutamide as an adjuvant treatment for localised prostate cancer with very high risk of recurrence (DASL-HiCaP).⁵

References

1. 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: February 2022.
2. Smith, RA, et al. Darolutamide and survival in metastatic hormone-sensitive prostate cancer. NEJM 2022 Feb 17, doi:10.1056/NEJMoa2119115 Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2119115 Last accessed: February 2022.
3. ClinicalTrials.Gov. ODM-201 in Addition to Standard ADT and Docetaxel in Metastatic Castration Sensitive Prostate Cancer (ARASENS). Available at: https://clinicaltrials.gov/ct2/show/NCT02799602 Last accessed: February 2022
4. ClinicalTrials.Gov. Darolutamide in Addition to ADT Versus ADT in Metastatic Hormone-sensitive Prostate Cancer (ARANOTE). Available at: https://clinicaltrials.gov/ct2/show/NCT04736199 Last accessed: February 2022
5. ClinicalTrials.Gov. Darolutamide Augments Standard Therapy for Localised Very High-Risk Cancer of the Prostate (DASL-HiCaP). Available at: https://clinicaltrials.gov/ct2/show/NCT04136353 Last accessed: February 2022
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7. 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 February 2022.
8. Cancer.Net. ASCO answers: Prostate Cancer. Available at: https://www.cancer.net/sites/cancer.net/files/asco_answers_guide_prostate.pdf  Last accessed: February 2022.
9. Cattrini, Castro, Lozano, Zanardi, Rubagotti, Boccardo and Olmos, 2019. Current Treatment Options for Metastatic Hormone-Sensitive Prostate Cancer. Cancers. 11(9), p.1355. 
10. Ritch, C. and Cookson, M., 2018. Recent trends in the management of advanced prostate cancer. F1000Research. 
11. NUBEQA® (darolutamide) 300 mg film-coated tables Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/11324 Last accessed: February 2022.
12. Data on File, Bayer UK plc.