"Patients at this stage of prostate cancer typically don't have symptoms of the disease. The overarching goals of treatment in this setting are to delay the spread of prostate cancer and limit the burdensome side effects of therapy," said Matthew Smith, M.D., Ph.D., Director of the Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center. "This approval marks an important new option for the prostate cancer community."In the U.S., over 73,000 men are estimated to be diagnosed with castration-resistant prostate cancer (CRPC) in 2019.2 About 40 percent of these patients have prostate cancer that has not spread to other parts of the body and is also associated with a rising prostate-specific antigen (PSA) level, despite a castrate testosterone level, which is known as nmCRPC.2,3 This is important because about one-third of men with nmCRPC go on to develop metastases within two years.4 PSA monitoring is important to identify patients and help offset undertreatment in men before the disease spreads.5,6
"With the approval of Nubeqa®, we now have a new therapy that extends MFS and allows physicians greater flexibility to treat men living with nmCRPC," said Robert LaCaze, Member of the Executive Committee of Bayer's Pharmaceuticals Division and Head of the Oncology Strategic Business Unit at Bayer. "Bayer is proud to take this latest step forward in the nmCRPC treatment landscape. Nubeqa is the newest addition to our prostate cancer portfolio and reflects Bayer's commitment to finding treatments for men at different stages along the prostate cancer continuum."In the ARAMIS trial, both arms showed a 9 percent discontinuation rate due to adverse reactions.1 The most frequent adverse reactions requiring discontinuation in patients who received Nubeqa included cardiac failure (0.4 percent), and death (0.4 percent).1 Adverse reactions occurring more frequently in the Nubeqa arm (≥2 percent over placebo) were fatigue (16 percent versus 11 percent), pain in extremity (6 percent versus 3 percent) and rash (3 percent versus 1 percent).1Nubeqa was not studied in women and there is a warning and precaution for embryo-fetal toxicity.1
Overall survival (OS) and time to pain progression were additional secondary efficacy endpoints.1 OS data were not yet mature at the time of final MFS analysis.1 The MFS result was supported by a delay in time to pain progression, defined as at least a 2-point worsening from baseline of the pain score on Brief Pain Inventory-Short Form or initiation of opioids, in patients treated with Nubeqa as compared to placebo.1 Pain progression was reported in 28 percent of all patients on study.1
Bayer has filed for approval of Nubeqa in the European Union (EU), Japan, and with other health authorities. Nubeqa is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.
Nubeqa will be available in oral tablets for adults.1 For more information, visit www.NUBEQA.com.
Clinical Trial Results
The FDA approval of Nubeqa® (darolutamide) is based on the ARAMIS trial, a randomized, double-blind, placebo-controlled, multi-center Phase III study, which evaluated the safety and efficacy of oral Nubeqa in patients with nmCRPC who were receiving a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy. In the clinical study, 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of Nubeqa orally twice daily or placebo plus ADT. Patients with a history of seizure were allowed in the study.1
The primary efficacy endpoint of the trial was MFS, defined as the time from randomization to the time of first evidence of BICR-confirmed distant metastasis or death due to any cause within 33 weeks after the last evaluable scan, whichever occurred first.1 Nubeqa plus ADT demonstrated a statistically significant improvement in MFS, with a median MFS of 40.4 months versus 18.4 months with placebo plus ADT [HR=0.41, 95% CI (0.34, 0.50), p<0.0001].1 OS and time to pain progression were additional secondary efficacy endpoints.1 OS data were not yet mature at the time of final MFS analysis.1 The MFS result was supported by a delay in time to pain progression, defined as at least a 2-point worsening from baseline of the pain score on Brief Pain Inventory-Short Form or initiation of opioids, in patients treated with Nubeqa as compared to placebo.1 Pain progression was reported in 28 percent of all patients on study.1
- Nubeqa® (darolutamide) tablets [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, July 2019.
- Bayer internal calculation based on Tesselon data (February 2018).
- Luo, Jia, Beer, Tomasz, Graff, Julie. Treatment of nonmetastatic castration-resistant prostate cancer. Oncology 2016;30(4):336-44.
- Kirby, Mike, Hirst, Ceri, Crawford. E. David. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract. 2011;65(11):1180-1192. doi:10.1111/j.1742-1241.2011.02799
- Thurtle, David R., Greenberg, David C., Lee, Lui S., Huang, Hong H., et al. Individual prognosis at diagnosis in nonmetastatic prostate cancer: Development and external validation of the PREDICT Prostate multivariable model. PLOS (2019) https://doi.org/10.1371/journal.pmed.1002758.
- Mayo Clinic. Prostate cancer screening: Should you get a PSA test? https://www.mayoclinic.org/tests-procedures/psa-test/in-depth/prostate-cancer/art-20048087. Accessed July 2019.
Watch: ARAMIS - Efficacy and Safety of Darolutamide in nmCRPC - Karim Fizazi
Read: ASCO GU 2019: ARAMIS: Efficacy and Safety of Darolutamide in Nonmetastatic Castration-Resistant Prostate Cancer