Nubeqa

Darolutamide

• Brand(s): Nubeqa
• Dosage Form/Strength: 300 mg tablet
• Effective date: June 8, 2021 (nmCRPC)
  Updated: March 8, 2024 (mCSPC)

High risk non-metastatic castration resistant prostate cancer (nmCRPC)

Initiation Criteria:

For the treatment of high-risk non-metastatic castration resistant prostate cancer (nmCRPC) in patients who meet all the following criteria:

1. Patient using darolutamide (Nubeqa) in combination with androgen deprivation therapy (ADT); AND

2. Has no detectable distant metastases as determined by CT, MRI, or technetium-99m bone scan; AND

3. Patient has castrate resistant disease based on meeting all the following indicia observed while on continuous ADT treatment or post orchiectomy:
   • Castrate serum testosterone levels; AND
   • Biochemical progression defined as three (3) prostate-specific antigen (PSA) rises at least 1 week apart, with the last PSA greater than 2ng/mL (if the patient has a history of antiandrogen use, the most recent PSA value must be obtained at least 4 weeks after anti-androgen withdrawal);

   AND

4. Patient is at high risk for developing metastatic disease based on a prostate-specific antigen doubling time (PSADT) of less than or equal to 10 months during continuous ADT.

5. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.

Exclusion Criteria:
Patients meeting one or more of the below exclusion criteria will not be funded.

• The patient received prior chemotherapy or immunotherapy for the treatment of prostate cancer, unless it was in the adjuvant or neoadjuvant setting completed more than 2 years previously.

• The patient has experienced disease progression on prior treatment with Erleada (apalutamide) or Xtandi (enzalutamide).

• The patient has a high risk for disease progression by other definitions (such as a high Gleason score 8-10, high PSA level at diagnosis, etc.) AND has not had a PSA progression in the non-metastatic setting.

Approved Dosage: 600 mg administered orally twice daily.

Notes:

1. The Ministry will fund only one of Nubeqa (darolutamide) or Erleada (apalutamide) or Xtandi (enzalutamide) in patients with non-metastatic castrate resistant prostate cancer.

2. While doses may be withheld or reduced to 300 mg twice daily to manage grade 3 toxicities until symptoms improve, treatment doses should be resumed at a dose of 600 mg twice daily.

3. Requests for Nubeqa in patients who initiated Erleada or Xtandi therapy in the nmCRPC setting and who have not had disease progression will be considered on a case-by-case basis.

4. Following progression on darolutamide in non-metastatic castrate resistant prostate cancer, the patient would not be eligible for darolutamide, apalatumide or enzalutamide in metastatic castrate resistant state.

Renewal Criteria:
Renewals will be considered in patients without evidence of radiographic disease progression or unacceptable toxicity while on Nubeqa therapy.

Approved Dosage: 600 mg administered orally twice daily.

Approval Duration of initials and renewals: 1 year

Metastatic castration sensitive prostate cancer

Initiation Criteria:

For the treatment of metastatic castration sensitive prostate cancer (mCSPC) in patients who meet all of the following criteria:

1. Darolutamide is used in combination with docetaxel and an androgen deprivation therapy (ADT)¹;
   AND
2. Metastatic lesions detected on technetium-99m bone scan, computed tomography (CT), and/or magnetic resonance imaging (MRI)²;
   AND
3. Castration sensitive as defined by the patient being treatment naïve to an ADT OR ADT initiated within the prior 6 months before start of therapy with darolutamide OR ADT was used in the neoadjuvant or adjuvant setting and the patient has not been treated with ADT for 12 months or more prior to start of darolutamide;
   AND
4. Has not experienced disease progression with another androgen receptor axis targeted therapy (ARAT) for castration sensitive prostate cancer;
   AND
5. Patient has good performance status and is deemed to be chemotherapy eligible.

¹ADT is not required for patients with bilateral orchiectomy.

²Positron emission tomography (PET) imaging results may be considered.

Definitions for the purpose of the EAP funding criteria:

• ADT – A first generation androgen deprivation therapy (e.g., goserelin, leuprolide, triptorelin, buserelin, degarelix)
• ARI – A second generation androgen receptor inhibitor (e.g., apalutamide, darolutamide, enzalutamide)
• ARAT – An androgen receptor axis targeted therapy (e.g., abiraterone, apalutamide, darolutamide, enzalutamide)

The following baseline levels are to be provided with the initial application:
i) Number of metastatic lesions on bone scan and in soft tissues
ii)Testosterone level
iii) Baseline (pre-treatment) PSA level
iv) Pre-treatment Gleason score (optional)

Notes:

1. Patients must not have received prior treatment with an androgen receptor axis–targeted therapy, chemotherapy, or immunotherapy for prostate cancer.
2. Patients who have previously progressed on an ARI for prostate cancer will not be eligible for darolutamide in mCSPC. The Ministry will fund only one of apalutamide or enzalutamide or darolutamide in patients with mCSPC.
3. Patients treated with apalutamide or enzalutamide as part of a clinical trial may be eligible for darolutamide in mCSPC and will be considered on a case-by-case basis.
4. Patients who progress on treatment with darolutamide, for mCSPC will not be eligible for another ARI in the metastatic castration resistant setting.
5. Patients who are currently on a treatment regimen with an ARAT for prostate cancer, must meet the initiation criteria if they wish to switch to publicly funded darolutamide for mCSPC.
6. Time limited funding consideration will be provided on a case-by case basis to add darolutamide in those patients who are using docetaxel in combination with ADT as long as there has been no progression and the treatment regimen has not been used for more than 6 months.

Approved Dosage for Initials and Renewals: 600 mg twice a day
(The dose of docetaxel used in combination with darolutamide should be based on the recommendations from the docetaxel product monograph or information from Ontario Health Cancer Care Ontario.)

Renewal Criteria:

Renewals will be considered in patients until disease progression (i.e. disease progression based on clinical, PSA and radiographic factors) or experiencing unacceptable toxicity due to darolutamide.

Exclusion Criteria: (Patients meeting any of the following will not be funded.)

• Patients who have previously experienced disease progression on darolutamide or another ARI used in the setting of prostate cancer.
• Darolutamide will not be funded as combination therapy with another ARAT.

Duration of initial and renewal approvals: 1 year

EAP Drug Request Form:

Standard Form for EAP Drug Requests