by Dr. C.H. Weaver M.D. updated 8/2022
Nubeqa (darolutamide), a novel androgen receptor inhibitor is improving treatment options for men with advanced prostate cancer. The phase III ARAMIS clinical trial published in The New England Journal of Medicine demonstrated that Nubeqa plus androgen deprivation therapy (ADT) significantly extends metastasis-free survival compared to ADT in non-metastatic castration-resistant prostate cancer.1,8,9 The ARASENS clinical trial demonstrated that Nubeqa added to ADT and Taxotere (docetaxel) chemotherapy improved outcomes for men with metastatic hormone-sensitive prostate cancer (mHSPC).11
About NUBEQA® (darolutamide)
NUBEQA is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.
About castration-resistant prostate cancer (CRPC)
Prostate cancer is the second most commonly diagnosed malignancy in men worldwide.2 An estimated 1.2 million men are diagnosed with prostate cancer, and about 358,000 die from the disease worldwide annually.3 Prostate cancer is the fifth leading cause of death from cancer in men.4 Prostate cancer results from the abnormal proliferation of cells within the prostate gland, which is part of a man's reproductive system.5 It mainly affects men over the age of 50, and the risk increases with age. Treatment options range from surgery to radiation treatment to therapy using hormone-receptor antagonists, i.e. substances that stop the formation of testosterone or prevent its effect at the target location.6 However, in nearly all cases, the cancer eventually becomes resistant to conventional hormone therapy.7
CRPC is an advanced form of the disease where the cancer keeps progressing even when the amount of testosterone is reduced to very low levels in the body. The field of treatment options for castration-resistant patients is evolving rapidly, but until recently, there have been no effective treatment options for CRPC patients who have rising PSA levels while on ADT and no detectable metastases. In men with progressive nmCRPC, a short PSA doubling time has been consistently associated with reduced time to first metastasis and death.7
About the ARAMIS Trial
The ARAMIS clinical trial is a randomized, phase III, multi-center, double-blind, placebo-controlled trial evaluating the safety and efficacy of oral Nubeqa in patients with non-metastatic CRPC who are currently being treated with ADT as standard of care and are at high risk for developing metastatic disease. 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of Nubeqa twice a day or placebo along with ADT.
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Results of the trial demonstrated that Nubeqa plus androgen deprivation therapy (ADT) significantly extended metastasis-free survival compared to ADT in non-metastatic castration-resistant prostate cancer. Nubeqa treated patients survived an average of 40.4 months without evidence of metastases compared to only 18.4 for individuals treated with ADT alone.1,8,9 Nubeqa resulted in a 31% reduction in the risk of death from prostate cancer.
About the ARASENS Trial
The ARASENS clinical directly compared Nubeqa plus (ADT) and Taxotere (docetaxel) chemotherapy in 1306 newly diagnosed men with metastatic hormone-sensitive prostate cancer (mHSPC) to treatment with ADT and Taxotere alone.13 The addition of Nubeqa to ADT and Taxotere
- Delayed time to pain progression
- Delayed time to first symptomatic skeletal event and time to initiation of subsequent systemic anti-neoplastic therapy1
Showed a statistically significant increase in overall survival with a reduction in the risk of death by 32.5%. The median survival duration with has not yet been reached and exceeds the 49 months reported for docetaxel alone.
The most common side effects experienced by patients who received the regimen included low blood counts, constipation, decreased appetite, rash, hemorrhage, increased weight, and hypertension.
The US FDA approved Nubeqa plus Docetaxel for treatment of metastatic Hormone-Sensitive Prostate Cancer in August of 2022 based on results of the ARASENS clinical trial.
- Fizazi, Karim; Shore, Neal; Tammela, Teuvo, et al. Darolutamide in Nonmetastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2019.
- GLOBOCAN 2018: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2018. Prostate Cancer. Accessed February 2019.
- American Cancer Society. What is Prostate Cancer?. Accessed February 2019.
- American Cancer Society. Prostate Cancer Risk Factors.. Accessed February 2019.
- National Cancer Institute. Hormone Therapy for Prostate Cancer.. Accessed February 2019.
- Nakazawa, Mary; Paller, Channing; Kyprianou, Natasha. Mechanisms of Therapeutic Resistance in Prostate Cancer. Curr Oncol Rep (2017) 19:13.
- Howard, Lauren; Moreira, Daniel M; DeHoedt, Amanda; Aronson, William J., et al. Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer. BJU Int 2017; 120: E80-E86.
- FDA approves darolutamide for non-metastatic castration-resistant prostate cancer
- NUBEQA® (darolutamide) tablets [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, January 2021.
- Smith M., Hussain M., Saad F. et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022.
- FDA approves darolutamide tablets for metastatic hormone-sensitive prostate cancer. News. FDA. August 5, 2022. Accessed August 5, 2022. https://bit.ly/3SqCCLw