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.

 

Median MFS was 40.4 months for NUBEQA + ADT (95% CI: 34.3-NE) 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).

 

OS was statistically significant; medians not estimable; HR: 0.69 (95% CI: 0.53-0.88); P=0.003.

 

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. The final analysis of OS and time to initiation of cytotoxic chemotherapy was event-driven and conducted after 254 OS events had occurred and 14 months after MFS analysis.1,2

 

PSA=prostate-specific antigen; ADT=androgen deprivation therapy; CI=confidence interval; NE=not estimable; HR=hazard ratio; 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.

DELAY METASTASIS, HELP PATIENTS LIVE LONGER WITHOUT PROGRESSION

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 (intent-to-treat).
*95% CI: 34.3-NE. 95% CI: 15.5-22.3.

  • Consistent results for MFS across patient subgroups1:
    • PSA doubling time (≤6 months or >6 months)
    • Prior use of bone-targeting agents (yes or no)
  • NUBEQA dosed at 600 mg twice daily results in PSA mean reduction >90% from baseline1

EXTEND OVERALL SURVIVAL, SO PATIENTS HAVE MORE TIME TO LIVE

Statistically significant overall survival1,3

Overall survival graph with statistically significant risk reduction in death vs ADT alone
  • OS was statistically significant despite3:
    • 31% (n=170) of patients in the ADT arm who crossed over to NUBEQA
    • 55% (n=307) of patients in the ADT arm who crossed over to NUBEQA or received another life-prolonging therapy prior to this analysis
  • With more than half of patients still alive at the final analysis, median OS was not reached. Median not estimable for both arms.3

Statistically significant delay in time to pain progression1,3

Secondary endpoint: HR: 0.65; 95% CI: 0.53-0.79; P<0.0001 (intent-to-treat)

35% Risk Reduction in time to pain progression with NUBEQA + ADT vs ADT alone | Nubeqa vs ADT
  • NUBEQA + ADT delayed median time to pain progression by nearly 59% vs ADT alone1
  • Time to pain progression was defined as at least a 2-point worsening from baseline of pain score on Brief Pain Inventory Short Form (a validated health-related quality-of-life instrument) or initiation of opioids and reported in 28% of all patients on study1,3

More time without cytotoxic chemotherapy1,3

Secondary endpoint: HR: 0.58; 95% CI: 0.44-0.76; P<0.0001

42% Risk Reduction in time to pain progression with NUBEQA + ADT vs ADT alone | Nubeqa vs ADT

*95% CI: 0.80-0.86.95% CI: 0.69-0.80.
Median: NE for both NUBEQA + ADT (n=955) and ADT alone (n=554).

Statistically significant results across all secondary endpoints1,3

Secondary endpoints chart displaying overall survival rates as well as time to progression, cytotoxic chemotherapy, and first symptomatic skeletal event.

*Median: NE for both arms.
Median: 40.3 mo, NUBEQA + ADT: 25.4 mo, ADT alone.

  • Delayed time to first symptomatic skeletal event: 52% risk reduction; HR: 0.48; 95% CI: 0.29-0.82; P=0.005.
    3% (n=29) of patients on NUBEQA + ADT vs 5% (n=28) of patients on ADT alone experienced a symptomatic skeletal event. Median not estimable for both arms.3

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 – 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.

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.; January 2021.
  • 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 N, Tammela TL, et al. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med. 2020;383(11):1040-1049.