IMPORTANT SAFETY INFORMATION

Embryo-Fetal Toxicity: Safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Continue reading »

NUBEQA (darolutamide) 300 mg tablets logo

IMPORTANT SAFETY INFORMATION

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. Continue reading »

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*Metastasis-free survival (MFS) was the primary endpoint, and overall survival (OS) was a key secondary endpoint.1

 

Median MFS was 40.4 months for NUBEQA + ADT (95% CI: 34.3-NR) and 18.4 months for ADT alone (95% CI: 15.5-22.3). NUBEQA + ADT vs ADT alone: HR: 0.41 (95% CI: 0.34-0.50; P<0.0001).1,2

 

At first analysis, OS data were not mature (57% of the required number of events). At final analysis, OS was statistically significant; HR: 0.69 (95% CI: 0.53-0.88), median not reached. P=0.003.1,3

 

The efficacy and safety of NUBEQA were assessed in a randomized, double-blind, placebo-controlled, international, multicenter, phase III study (ARAMIS) in nmCRPC patients with a PSA doubling time of ≤10 months. 1509 patients were randomized 2:1 to receive either 600 mg NUBEQA twice daily (n=955) or matching placebo (n=554). All patients received concurrent ADT (treatment with GnRH analog or previous bilateral orchiectomy). The primary endpoint was MFS, defined as the time from randomization to the time of first evidence of BICR-confirmed distant metastasis or death from any cause within 33 weeks after the last evaluable scan, whichever occurred first. Treatment continued until radiographic disease progression, as assessed by CT, MRI, 99mTc bone scan by BICR, unacceptable toxicity, or withdrawal.1,2

 

ADT=androgen deprivation therapy; CI=confidence interval; NR=not reached; HR=hazard ratio; PSA=prostate-specific antigen; GnRH=gonadotropin-releasing hormone; BICR=blinded independent central review; CT=computed tomography; MRI=magnetic resonance imaging.

INDICATION

NUBEQA® (darolutamide) is an androgen receptor inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer.

40 MONTHS MFS ACHIEVED with NUBEQA + ADT

More than double the median MFS vs ADT alone1,2

Nubeqa + ADT vs ADT Alone

HR: 0.41; 95% CI: 0.34-0.50; P<0.0001
95% CI: 34.3-NR. 95% CI: 15.5-22.3.

  • MFS results were consistent across patient subgroups for1
    • PSA doubling time (≤6 months or >6 months)
    • Prior use of bone-targeting agents (yes or no)

FINAL ANALYSIS OF OS SECONDARY ENDPOINT

Now with statistically significant OS3

Overall survival graph with statistically significant risk reduction in death vs ADT alone
  • Secondary endpoint analysis: Secondary endpoints were evaluated in a hierarchical order, with a significance level of 0.05 split between the primary analysis and final analysis (planned to occur after 240 deaths from any cause). The OS endpoint was used to determine the alpha spend and significance threshold for each of the secondary endpoints2
  • Previously, OS data were not mature at first analysis (57% of the required number of events), which prevented other secondary endpoints from being formally evaluated1

Statistically significant delay in time to pain progression3

Nubeqa vs ADT
  • NUBEQA + ADT delayed time to pain progression by 14.9 months over ADT alone3
  • 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 the Brief Pain Inventory-Short Form or initiation of opioids, in men treated with NUBEQA + ADT as compared to ADT alone. Pain progression was reported in 28% of all men in the first analysis. No additional data for pain progression were collected beyond the first analysis1,3

HR: 0.41; 95% CI: 0.34-0.50; P<0.0001
95% CI: 34.3-NR. 95% CI: 15.5-22.3.

Statistically significant risk reduction in other secondary endpoints3

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Summary of secondary endpoints3

Secondary endpoints chart displaying overall survival rates as well as time to progression, cytotoxic chemotherapy, and first symptomatic skeletal event.
  • Previously, OS data were not mature at first analysis (57% of the required number of events), which prevented other secondary endpoints from being formally evaluated

INDICATION

NUBEQA® (darolutamide) is an androgen receptor inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer.

IMPORTANT SAFETY INFORMATION

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.

Adverse Reactions
Serious adverse reactions occurred in 25% of patients receiving NUBEQA and in 20% of patients receiving placebo. Serious adverse reactions in ≥ 1 % of patients who received NUBEQA were urinary retention, pneumonia, and hematuria. Overall, 3.9% of patients receiving NUBEQA and 3.2% of patients receiving placebo died from adverse reactions, which included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%) for NUBEQA.

Adverse reactions occurring more frequently in the NUBEQA arm (≥2% over placebo) were fatigue (16% vs. 11%), pain in extremity (6% vs. 3%) and rash (3% vs. 1%).

Clinically significant adverse reactions occurring in ≥ 2% of patients treated with NUBEQA included ischemic heart disease (4.0% vs. 3.4% on placebo) and heart failure (2.1% vs. 0.9% on placebo).

Drug Interactions
Effect of Other Drugs on NUBEQA – Concomitant use of NUBEQA with a combined P-gp and strong or moderate CYP3A4 inducer decreases darolutamide exposure, which may decrease NUBEQA activity. Avoid concomitant use of NUBEQA with combined P-gp and strong or moderate CYP3A4 inducers.

Concomitant use of NUBEQA with a combined P-gp and strong CYP3A4 inhibitor increases darolutamide exposure, which may increase the risk of NUBEQA adverse reactions. Monitor patients more frequently for NUBEQA adverse reactions and modify NUBEQA dosage as needed.

Effects of NUBEQA on Other Drugs – NUBEQA is an inhibitor of breast cancer resistance protein (BCRP) transporter. Concomitant use of NUBEQA increases the exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use with drugs that are BCRP substrates where possible. If used together, monitor patients more frequently for adverse reactions, and consider dose reduction of the BCRP substrate drug. Consult the approved product labeling of the BCRP substrate when used concomitantly with NUBEQA.

For important risk and use information about 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:

  • NUBEQA (darolutamide) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; July 2019.
  • Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019;380(13):1235-1246.
  • Fizazi K, Shore ND, Tammela T, et al. Overall survival results of the phase III ARAMIS study of darolutamide added to androgen deprivation therapy for non-metastatic castration resistant prostate cancer. Presented at: 2020 ASCO Annual Meeting; May 29-31, 2020.