FINAL RESULTS FOR
Metastasis-free survival (MFS) was the primary endpoint, and overall survival (OS) was a key secondary endpoint.1
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For your patient with metastatic hormone-sensitive prostate cancer (mHSPC) or non-metastatic castration-resistant prostate cancer (nmCRPC)
Extend patient survival with NUBEQA1-4
NUBEQA IS THE ONLY ARI THAT REDUCED THE RISK OF DEATH BY >30% ACROSS mHSPC and
- In mHSPC, NUBEQA is the only ARI approved in combination with docetaxel + ADT that significantly extends OS beyond docetaxel + ADT; HR: 0.68; 95% CI: 0.57-0.80; P<0.0001
- In nmCRPC, NUBEQA + ADT reduced the risk of death by nearly a third vs ADT alone (OS was a secondary endpoint); HR: 0.69; 95% CI: 0.53-0.88; P=0.003. MFS was the primary endpoint
ARASENS Study Design: 1305 mHSPC patients on ADT* with docetaxel who received ADT within 12 weeks before study entry were randomized 1:1 and treated with concurrent 600 mg NUBEQA twice daily (n=651) or placebo (n=654) in a multicenter, double-blind, phase III trial. Concomitant docetaxel was administered at 75 mg/m2 every 21 days for 6 cycles within 6 weeks of starting NUBEQA or placebo. OS was statistically significant for the NUBEQA arm vs placebo arm; HR: 0.68; 95% CI: 0.57-0.80; P<0.0001.1,2
ARAMIS Study Design: 1509 nmCRPC patients on ADT* with a PSA doubling time of ≤10 months were randomized 2:1 to receive concurrent 600 mg NUBEQA twice daily (n=955) or placebo (n=554) in a multicenter, double-blind, phase III trial. Treatment continued until radiographic disease progression as assessed by CT, MRI, 99mTc bone scan by BICR, unacceptable toxicity, or withdrawal. MFS was statistically significant with a median of 40.4 months vs 18.4 months for placebo; HR: 0.41; 95% CI: 0.34-0.50; P<0.0001. The final analysis of OS was statistically significant vs placebo; HR: 0.69; 95% CI: 0.53-0.88; P=0.003. MFS was the primary endpoint and OS was a key secondary endpoint.1,3,4
Concomitant GnRH analog or prior bilateral orchiectomy.
ARI=androgen receptor inhibitor; ADT=androgen deprivation therapy; OS=overall survival; HR=hazard ratio; CI=confidence interval; MFS=metastasis-free survival; CRPC=castration-resistant prostate cancer; PSA=prostate-specific antigen; CT=computed tomography; MRI=magnetic resonance imaging; BICR=blinded independent central review; GnRH=gonadotropin-releasing hormone.
NUBEQA® (darolutamide) is an androgen receptor inhibitor indicated for the treatment of adult patients with:
- Non-metastatic castration-resistant prostate cancer (nmCRPC)
- Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel
Important Safety Information
Warnings & Precautions
Ischemic Heart Disease – In a study of patients with nmCRPC (ARAMIS), ischemic heart disease occurred in 3.2% of patients receiving NUBEQA versus 2.5% receiving placebo, including Grade 3-4 events in 1.7% vs. 0.4%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA vs. 0.2% receiving placebo. In a study of patients with mHSPC (ARASENS), ischemic heart disease occurred in 2.9% of patients receiving NUBEQA with docetaxel vs. 2% receiving placebo with docetaxel, including Grade 3-4 events in 1.3% vs. 1.1%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA with docetaxel vs. 0% receiving placebo with docetaxel. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue NUBEQA for Grade 3-4 ischemic heart disease.
Seizure – In ARAMIS, Grade 1-2 seizure occurred in 0.2% of patients receiving NUBEQA vs. 0.2% receiving placebo. Seizure occurred 261 and 456 days after initiation of NUBEQA. In ARASENS, seizure occurred in 0.6% of patients receiving NUBEQA with docetaxel, including one Grade 3 event, vs. 0.2% receiving placebo with docetaxel. Seizure occurred 38 to 340 days after initiation of NUBEQA. It is unknown whether anti-epileptic medications will prevent seizures with NUBEQA. Advise patients of the risk of developing a seizure while receiving NUBEQA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others. Consider discontinuation of NUBEQA in patients who develop a seizure during treatment.
Embryo-Fetal Toxicity – Safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose.
In ARAMIS, serious adverse reactions occurred in 25% of patients receiving NUBEQA vs. 20% of patients receiving placebo. Serious adverse reactions in ≥1% of patients who received NUBEQA included urinary retention, pneumonia, and hematuria. Fatal adverse reactions occurred in 3.9% of patients receiving NUBEQA vs. 3.2% of patients receiving placebo. Fatal adverse reactions in patients who received NUBEQA included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%). The most common adverse reactions (>2% with a ≥2% increase over placebo), including laboratory test abnormalities, were increased AST, decreased neutrophil count, fatigue, increased bilirubin, pain in extremity, and rash. Clinically relevant adverse reactions occurring in ≥2% of patients treated with NUBEQA included ischemic heart disease and heart failure.
In ARASENS, serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel vs. 42% of patients receiving placebo with docetaxel. Serious adverse reactions in ≥2% of patients who received NUBEQA with docetaxel included febrile neutropenia (6%), decreased neutrophil count (2.8%), musculoskeletal pain (2.6%), and pneumonia (2.6%). Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel vs. 4% of patients receiving placebo with docetaxel. Fatal adverse reactions in patients who received NUBEQA included COVID-19/COVID-19 pneumonia (0.8%), myocardial infarction (0.3%), and sudden death (0.3%). The most common adverse reactions (≥10% with a ≥2% increase over placebo with docetaxel) were constipation, decreased appetite, rash, hemorrhage, increased weight, and hypertension. The most common laboratory test abnormalities (≥30%) were anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, increased AST, increased ALT, and hypocalcemia. Clinically relevant adverse reactions in <10% of patients who received NUBEQA with docetaxel included fractures, ischemic heart disease, seizures, and drug-induced liver injury.
Effect of Other Drugs on NUBEQA – Combined P-gp and strong or moderate CYP3A4 inducers decrease NUBEQA exposure, which may decrease NUBEQA activity. Avoid concomitant use.
Combined P-gp and strong CYP3A4 inhibitors increase NUBEQA exposure, which may increase the risk of NUBEQA adverse reactions. Monitor more frequently and modify NUBEQA dose as needed.
Effects of NUBEQA on Other Drugs – NUBEQA inhibits breast cancer resistance protein (BCRP) transporter. Concomitant use increases exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use where possible. If used together, monitor more frequently for adverse reactions, and consider dose reduction of the BCRP substrate.
NUBEQA inhibits OATP1B1 and OATP1B3 transporters. Concomitant use may increase plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor more frequently for adverse reactions and consider dose reduction of these substrates.
Review the Prescribing Information of drugs that are BCRP, OATP1B1, and OATP1B3 substrates when used concomitantly with NUBEQA.
Please see the full Prescribing Information.
You are encouraged to report side effects or quality complaints of products to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.
References: 1. NUBEQA (darolutamide) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; August 2022. 2. Smith MR, Hussain M, Saad F, et al; ARASENS Trial Investigators. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022;386(12):1132-1142. 3. Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019;380(13):1235-1246. 4. Fizazi K, Shore N, Tammela TL, et al. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med. 2020;383(11):1040-1049. 5. Smith MR, Saad F, Chowdhury S, et al. Apalutamide and overall survival in prostate cancer. Eur Urol. 2021;79(1):150-158. 6. Sternberg CN, Fizazi K, Saad F, et al. Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2020;382(23):2197-2206.