NUBEQA^® is funded across Canada

Coverage in Alberta: Outpatient Cancer Drug Benefit Program

1. Patient Eligibility:
   • Darolutamide + ADT for nmCRPC patients at high risk of developing metastases (PSADT ≤10 months during continuous ADT).
   • Patients may receive only one of darolutamide, apalutamide, or enzalutamide in this setting, and switching is allowed only in cases of intolerance, not disease progression.
2. Prescriber Requirements:
   • Written authorization is required by named physicians listed in the Outpatient Cancer Drug Benefit Program.

1. Patient Eligibility:
   • Darolutamide used in combination with docetaxel and androgen deprivation therapy (ADT) for the treatment of patients with mCSPC.
   • Has no prior ADT in the metastatic setting, or within 6 months of beginning ADT for metastatic disease, or more than 1 year after completing adjuvant ADT in the non-metastatic setting.
   • Patients are not eligible if they have received prior treatment with an androgen receptor-axis-targeted therapy (ARAT), chemotherapy, or immunotherapy for prostate cancer.
   • Patients should be chemotherapy-eligible and have good performance status.
2. Clinical Notes:
   • Patients unable to tolerate docetaxel (with no progression) are eligible to continue with darolutamide + ADT.
   • Patients unable to tolerate darolutamide (with no disease progression) may switch to a different ARAT + docetaxel + ADT or an ARAT + ADT combination.
3. Prescriber Requirements:
   • Named physicians listed in the Outpatient Cancer Drug Benefit Program may submit written authorization directly to Alberta Health Services.

Coverage in British Columbia: BC Cancer Drug Benefit List

1. Patient Eligibility:
   • Diagnosis of nmCRPC with no radiologic evidence of metastases within the last 6 months (negative bone scan, negative CT of pelvis, abdomen, chest).
     • Exception: pelvic lymph nodes <2cm in short axis below the aortic bifurcation)
   • No prior chemotherapy for nmCRPC, and
   • PSA doubling time (PSADT) of ≤10 months
   • ECOG performance status 0-2.
2. Prescriber Requirements:
   • Completion and approval of the BC Cancer Compassionate Access Program (CAP) application is required prior to treatment.
3. Claim Notes:
   • Patients with nmCRPC are eligible to receive any one of the following, but not their sequential use: apalutamide OR darolutamide OR enzalutamide.
   • Patients who have progressed to metastatic disease on darolutamide are eligible to receive all of the following: docetaxel, cabazitaxel, radium (in mCRPC); NOT eligible for enzalutamide or abiraterone at progression while on darolutamide.
4. Exclusions:
   • Metastatic prostate cancer
   • Prior treatment for nmCRPC with apalutamide or enzalutamide
   • Prior chemotherapy for nmCRPC 

1. Patient Eligibility: 

   • Patients must have metastatic castration sensitive prostate cancer (mCSPC).
   • No prior systemic treatment of metastatic prostate cancer (excluding ADT*).
   • A BC Cancer “Compassionate Access Program” (CAP) request must be approved prior to treatment.
   • Patients should have fitness for treatment containing docetaxel, and
   • Good performance status, and
   • Total bilirubin less than ULN, AST/ALT less than 5 x ULN, alkaline phosphatase less than 6 x ULN.

   *Previous ADT permitted if the patient received: 

   • Less than 6 months of ADT for mCSPC immediately prior to starting this protocol, and
   • No ADT for adjuvant treatment of non-metastatic prostate cancer within 1 year of starting this protocol.
2. Prescriber Requirement: for eligible new mCSPC patients initiating NUBEQA in combination with docetaxel, submissions may be made directly to BCCA.
3. Notes:
   • Patients currently being treated with GUPDOCADT who have not progressed may switch to UGUMCSPDD if all other eligibility criteria are met.
   • Patients with mCSPC are eligible to receive any of the following, but not their sequential use:
     • Apalutamide (GUMCSPAPA),
     • Enzalutamide (GUMCSPENZ)
     • Abiraterone (GUMCSPABI), or
     • Darolutamide + DOCEtaxel (UGUMCSPDD)
   • Patients treated with darolutamide for mCSPC who develop castration resistant disease are NOT eligible to receive abiraterone (UGUPABI) or enzalutamide (UGUPENZ).
4. Exclusions:
   • Patients must not have completed adjuvant treatment (i.e., prior UGUPAJABI) for prostate cancer less than 1 year prior to initiation of UGUMCSPDD.
   • Initiation of darolutamide without docetaxel is not funded.
5. Tests
   • Baseline: CBC & Diff, platelets, creatine, sodium, potassium, total bilirubin, ALT, alkaline phosphatase, GGT, albumin, INR, PSA, testosterone, blood pressure, ECG (if clinically indicated).
   • Cycle 1-6 (Docetaxel and Darolutamide Combination Treatment):
     • Before each docetaxel treatment: CBC & Diff, platelets, PSA (PSA required every 3 weeks, but results do not have to be available to proceed with treatment).
     • Before docetaxel Cycle 4, and anytime if clinically indicated: total bilirubin, ALT, alkaline phosphatase, LDH (see Precaution #5 for guidelines).
   • Cycle 7 Onwards (Darolutamide Treatment):
     • At each physician visit: PSA, testosterone, blood pressure.
     • If clinically indicated: ECG, calcium, albumin, total bilirubin, ALT, random glucose, HbA1c, creatine, sodium, potassium, TSH, INR.
6. Premedication:
   • Cycles 1-6 (Docetaxel and Darolutamide Combination Treatment):
     • Dexamethasone 8 mg PO BID for 3 days, starting 1 day prior to each docetaxel administration; patient must receive a minimum of 3 doses pretreatment.
     • Additional antiemetics not usually required.
     • Docetaxel-induced onycholysis and cutaneous toxicity of the hands may be prevented by wearing frozen gloves starting 15 minutes before docetaxel infusion until 15 minutes after completion; gloves should be changed after 45 minutes of wearing to ensure they remain cold throughout the infusion.
   • Cycle 7 Onwards (Darolutamide Treatment)
     • No premedication or antiemetics required.

1. Patient Eligibility: 
   • Diagnosis of metastatic castration sensitive prostate cancer (mCSPC).
   • No prior systemic therapy for prostate cancer. Previous androgen deprivation therapy (ADT) is permitted if: 
     • Less than 6 months of ADT was received for mCSPC immediately prior to initiating this protocol,
       and
     • No ADT was given as adjuvant treatment for non‑metastatic prostate cancer within 1 year of starting this protocol.
   • Patients have a good performance status.
2. Notes: 
   • Patients with mCSPC are eligible to receive any of the following, but not their sequential use: 
     • Apalutamide (GUMCSPAPA), 
     • Abiraterone (GUMCSPABI), 
     • Darolutamide (GUMCSPDAR), 
     • Darolutamide with DOCEtaxel (UGUMCSPDD), or 
     • Enzalutamide (GUMCSPENZ).
   • Patients treated with darolutamide for mCSPC who develop castration resistant disease are NOT eligible to receive abiraterone (UGUPABI, UGUPAVOABI, UGUPAVNABI) or enzalutamide (UGUPENZ).
3. Tests:
   • Baseline: CBC & Diff, albumin, total bilirubin, alkaline phosphatase, GGT, INR, ALT, creatinine, sodium, potassium, PSA, testosterone, blood pressure.
   • Baseline if clinically indicated: ECG.
   • Each time seen by physician: PSA, blood pressure.
   • If clinically indicated: albumin, total bilirubin, INR, ALT, creatinine, sodium, potassium, TSH, ECG, HbA1c, calcium, random glucose, testosterone.

Coverage in Manitoba: Exception Drug Status

1. Patient Eligibility:
   • Darolutamide in combination with ADT for the treatment of nmCRPC patients at high risk of developing metastases (PSADT of ≤10 months during continuous ADT).
   • Castration-resistant disease according to the Prostate Cancer Working Group 2 (PCWG2) criteria.
   • Absence of metastases (determined by negative CT and bone scan).
   • Patient has a good performance status.
2. Prescriber Requirements: Authorized prescribers will be required to complete and submit the Exception Drug Status request.
3. Clinical Notes: Treatment should continue until unacceptable toxicity or radiographic disease progression.

1. Patient Eligibility:
   • Darolutamide in combination with docetaxel and ADT for the treatment of patients with mCSPC.
   • Patients are eligible for chemotherapy.
   • Have a good performance status.
   • Must not have received prior treatment with androgen receptor axis-targeted therapy, chemotherapy, or immunotherapy for prostate cancer.
   • Must not have received ADT in the metastatic setting for more than 6 months, or within 1 year of completing adjuvant ADT in the nonmetastatic setting.
2. Prescriber Requirements:
   • For eligible new mCSPC patients initiating NUBEQA in combination with docetaxel, submissions may be made directly to Manitoba formulary.    

Coverage in New Brunswick: Special Authorization

1. Patient Eligibility:
   • Darolutamide + ADT for the treatment of nmCRPC patients at high risk of developing metastases (PSADT of ≤10 months during continuous ADT).
2. Prescriber Requirements:
   • Authorized prescribers are required to complete and submit a form to request coverage through special authorization.
3. Renewal Criteria:
   • Written confirmation that the patient has responded to treatment and that there is no evidence of radiographic disease progression.
4. Clinical Notes:
   • Castration-resistance must be demonstrated during continuous ADT; defined as a minimum of three rises in PSA, measured at least one week apart, with the last PSA greater than 2 mcg/L.
   • Castrate levels of testosterone must be maintained throughout treatment with darolutamide.
   • Patients must have a good performance status.
   • Treatment should be discontinued upon radiographic disease progression or unacceptable toxicity.
5. Claim Notes:
   • Requests not considered for patients who experience disease progression on apalutamide or enzalutamide
   • Initial approval period: 1 year
   • Renewal approval period: 1 year 

Coverage in Newfoundland and Labrador: Special Authorization

1. Patient Eligibility:
   • Darolutamide + ADT for the treatment of patients with nmCRPC.
   • Have no detectable distant metastases by either CT, MRI, or technetium-99m bone scan.
   • PSADT of ≤10 months during continuous ADT (i.e., high risk of developing metastases).
   • Patients should have good performance status.
2. Renewal Criteria:
   • Written confirmation that the patient has responded to treatment and there is no evidence of radiographic disease progression.
   • Initial approval period: 1 year
   • Renewal approval period: 1 year
3. Clinical Notes:
   • Castration-resistance must be demonstrated during continuous ADT and is defined as three PSA rises measured at least one week apart, with the last PSA >2 ng/mL.
   • Castrate levels of testosterone must be maintained.
   • Patients with N1 disease, pelvic lymph nodes <2cm in short axis located below the aortic bifurcation are eligible for darolutamide.
   • Treatment should be discontinued upon radiographic disease progression or unacceptable toxicity.
4. Claim Notes:
   • Darolutamide will not be funded for patients who experience disease progression on apalutamide or enzalutamide.
   • Patients receiving darolutamide for the treatment of nmCRPC will be eligible for funding of abiraterone at the time of disease progression to mCRPC.
   • Enzalutamide is not funded for patients who experience disease progression to mCRPC while on darolutamide.
   • Either abiraterone or enzalutamide may be used to treat mCRPC in patients who discontinued darolutamide in the non-metastatic setting due to intolerance without disease progression.

Coverage by NIHB: Limited Use Benefit

1. Criteria for initial 12-month coverage: for the treatment of non-metastatic castration-resistant* prostate cancer patients (nmCRPC) who meet all the following criteria:
   • used in combination with androgen deprivation therapy (ADT); and
   • are at high risk** of developing metastases; and
   • have no detectable distant metastases by either CT, MRI or technetium-99m bone scan; and
   • have a good ECOG performance status (0 or 1)
2. Criteria for renewal (every 12 months):
   There is no objective evidence of radiographic disease progression or unacceptable toxicity.

*Castration-resistance is according to the prostate cancer working group 2 (PCWG2) criteria used in the ARAMIS trial.
**High risk is defined as a prostate-specific antigen doubling time (PSADT) of ≤10 months during continuous ADT.

1. Patient Eligibility: for the treatment of mCSPC patients who meet all of the following criteria
   • Used in combination with ADT, with or without docetaxel; and
   • Patients are castration-sensitive (i.e., no prior ADT or within 6 months of beginning ADT); and
   • Have a good performance status.
   • Have not received prior treatment with an androgen receptor axis-targeted therapy (apalutamide or enzalutamide), chemotherapy, or immunotherapy for prostate cancer; and
   • Have not received ADT in metastatic setting for more than 6 months, OR within 1 year of completing adjuvant ADT in the non-metastatic setting.
   • (If applicable) switches from other androgen receptor pathway inhibitors (ARPIs) to NUBEQA, due to intolerance without disease progression, are permitted.
2. Prescriber Requirements: submit reimbursement requests directly to NIHB.
3. Criteria for Renewal (Every 12 months):
   • No objective evidence of radiographic disease progression or unacceptable toxicity. 

Coverage in Nova Scotia: Exception Drug Status

1. Patient Eligibility:
   • Darolutamide + ADT for the treatment of nmCRPC patients who are at high risk of developing metastases.^†
   • Have a good performance status.
   • Treatment should continue until unacceptable toxicity or radiographic disease progression.
2. Prescriber Requirements: authorized prescribers are required to complete and submit an Exception Drug Status request.
3. Clinical Notes:
   • Castration-resistance must be demonstrated during continuous ADT and is defined as three PSA rises, measured at least one week apart, with the last PSA >2 ng/mL.
   • No detectable distant metastases, as determined by CT, MRI, or technetium-99m bone scan.
   • Castrate level of testosterone is maintained.
   • Patients with N1 disease, pelvic lymph node <2cm in short axis located below the aortic bifurcation are eligible for darolutamide.
4. Claim Notes:
   • Darolutamide will not be funded for patients who experience disease progression on apalutamide or enzalutamide.
   • Patients receiving darolutamide for the treatment of nmCRPC will be
     eligible for funding of
     abiraterone
     at the time of disease progression to mCRPC.
   • Enzalutamide is
     NOT
     funded for patients who experience disease progression to mCRPC while on darolutamide.
   • Either abiraterone or enzalutamide may be used to treat mCRPC in patients who discontinued darolutamide in the non-metastatic setting due to intolerance without disease progression.

† High risk of developing metastases is defined as a prostate-specific antigen (PSA) doubling time of ≤10 months during continuous ADT.

1. Patient Eligibility:
   • For the treatment of patients with mCSPC when used in combination with ADT OR in combination with docetaxel and ADT.
   • Patients should have good performance status.
   • Patients should have had no prior ADT in the metastatic setting, or be within 6 months of initiating ADT in the metastatic setting with no disease progression.
   • Patients will be eligible if they received ADT in the non-metastatic setting as long as at least one-year interval has passed since completion.
2. Prescriber Requirements: eligible new mCSPC patients initiating NUBEQA + ADT may be submitted directly to Nova Scotia Formulary for public coverage.
3. Clinical Notes:
   • Treatment should continue until disease progression or unacceptable toxicity.
4. Funding Notes:
   • Darolutamide will not be funded for patients who experience disease progression on apalutamide or enzalutamide.

Coverage in Ontario: Exceptional Access Program

1. Initiation Criteria:
   • Patients who are using darolutamide in combination with ADT; AND
   • Has no detectable distant metastases as determined by CT, MRI, or technetium-99m bone scan.
   • Have castrate resistant disease, as evidenced by the following criteria while on continuous ADT treatment or post orchiectomy:
     • Castrate serum testosterone levels; AND
     • Biochemical progression, defined as three PSA rises, measured at least 1 week apart, with the last PSA greater than 2 ng/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
   • Patients are at high risk of developing metastatic disease (based on PSADT of ≤10 months during continuous ADT).
   • Have an Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
2. Exclusion Criteria (patient meeting one or more of the below criteria will not be funded):
   • Patients who 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.
   • Patients who have experienced disease progression on prior treatment with Erleada (apalutamide) or Xtandi (enzalutamide).
   • Patients who have a high risk for disease progression by other definitions (i.e., a high Gleason score 8-10, high PSA level at diagnosis, etc.) AND have not had a PSA progression in the non-metastatic setting
3. Claim Notes:
   • The Ministry will fund only one of NUBEQA (darolutamide), Erleada (apalutamide), or Xtandi (enzalutamide) in patients with nmCRPC.
   • Request 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.
   • Following progression on darolutamide in nmCRPC, patients will not be eligible for darolutamide, apalutamide, or enzalutamide in the mCRPC setting.
4. Dosage Modifications:
   • Approved dosage: 600 mg orally twice daily
   • Dosage may be temporarily reduced to 300 mg twice daily to manage Grade 3 toxicities. Resume 600 mg twice daily once symptoms improve.
5. Renewal Criteria:
   • Renewals will be considered in patients without evidence of radiographic disease progression or unacceptable toxicity while on NUBEQA therapy.
   • Approval duration:
     • Initial approval: 1 year
     • Renewal approval: 1 year 

1. Patient Eligibility:
   • Darolutamide is used in combination with ADT (ADT is not required for patients with bilateral orchiectomy); AND
   • Metastatic lesions detected on technium-99m bone scan, CT, and/or MRI (PET imaging results may be considered); AND
   • Castration sensitive, defined as:
     • Patient being treatment-naïve to ADT, OR
     • ADT initiated within the prior 6 months before the start of therapy with darolutamide, OR
     • ADT used in the neoadjuvant or adjuvant setting, and the patient has not been treated with ADT for 12 months or more prior to the start of darolutamide.
   • Has not experienced disease progression with another androgen receptor axis-targeted therapy (ARAT) for castration sensitive prostate cancer; AND
   • Patients have good performance status.
2. Prescriber Requirements: Submit authorization form directly to the Exceptional Access Program (EAP).
3. Funding Notes:
   • Patients who have previously progressed on an androgen receptor inhibitor (ARI) for prostate cancer will not be eligible for darolutamide in mCSPC.
   • The Ministry will fund only one of apalutamide, enzalutamide, or darolutamide in patients with mCSPC.
   • Patients treated with apalutamide or enzalutamide as part of a clinical trial may be eligible for darolutamide and will be considered on a case-by-case basis.
   • Patients who progress on treatment with darolutamide for mCSPC will not be eligible for another ARI in the metastatic castration resistant setting.
   • 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.
4. Approved dosage for initiation and renewals: 600 mg twice daily
5. Renewal Criteria:
   • Renewals will be considered for patients until disease progression (i.e. disease progression based on clinical, PSA and radiographic factors) or the occurrence of unacceptable toxicity.   
     • Duration of initial approval: 1 year
     • Duration of renewed approval: 1 year
6. 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.

1. Initiation Criteria:
   • Darolutamide is used in combination with docetaxel and ADT (ADT is not required for patients with bilateral orchiectomy); AND
   • Metastatic lesions detected on technetium-99m bone scan, CT, and/or MRI scan (PET imaging results may be considered); AND
   • Castration sensitive, defined as:
     • Patient being treatment-naïve to ADT, OR
     • ADT initiated within the prior 6 months before the start of therapy with darolutamide, OR
     • ADT used in the neoadjuvant or adjuvant setting, and the patient has not been treated with ADT for 12 months or more prior to the start of darolutamide.
   • Has not experienced disease progression with another androgen receptor axis targeted therapy (ARAT) for castration sensitive prostate cancer; AND
   • Patients have good performance status and are chemotherapy-eligible.
2. Prescriber Requirements:
   • For eligible new mCSPC patients initiating NUBEQA with docetaxel, submission may be made directly to EAP.
3. Initial Application Requirements: the following baseline levels are to be provided with the initial application:
   • Number of metastatic lesions on bone scan and in soft tissues
   • Testosterone level
   • Baseline (pre-treatment) PSA level
   • Pre-treatment Gleason score (optional)
4. Notes:
   • Patients must not have received prior treatment with an androgen receptor axis–targeted therapy, chemotherapy, or immunotherapy for prostate cancer.
   • 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.
   • 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.
   • Patients who progress on treatment with darolutamide, for mCSPC will not be eligible for another ARI in the metastatic castration resistant setting.
   • 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.
   • 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.
5. Approved Dosage for Initial and Renewals: 600 mg twice daily
   • 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.
6. Renewal Criteria & Duration:
   • Renewals will be considered for patients until disease progression (i.e. disease progression based on clinical, PSA and radiographic factors) or the occurrence of unacceptable toxicity due to darolutamide.
   • Duration of initial and renewal approvals: 1 year.
7. 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.

Coverage in Prince Edward Island: Restricted Benefit

1. Patient Eligibility:
   • Darolutamide + ADT for the treatment of nmCRPC patients at high risk of developing metastases*; and
   • Have a good performance status,
   • Patients should have no detectable distant metastases by either CT, MRI, or technetium-99m bone scan.
   • Castrate levels of testosterone must be maintained.
2. Clinical Notes:
   • Castration-resistance must be demonstrated during continuous ADT and is defined as 3 PSA rises, measured at least one week apart, with the last PSA >2 ng/mL.
   • Patients with N1 disease, pelvic lymph nodes < 2cm in short axis, located below the aortic bifurcation are eligible for darolutamide.
   • Patients should have a good performance status.
   • Treatment should be discontinued upon radiographic disease progression or unacceptable toxicity.
3. Funding Notes:
   • Darolutamide will not be funded for patients who experience disease progression on apalutamide or enzalutamide.
   • Patients receiving darolutamide for the treatment of nmCRPC will be eligible for funding of abiraterone at the time of disease progression to mCRPC.
   • Enzalutamide is not funded for patients who experience disease progression to mCRPC while on darolutamide.
   • Either abiraterone or enzalutamide may be used to treat mCRPC in patients who discontinued darolutamide in the non-metastatic setting due to intolerance without disease progression.

*High risk of developing metastases is defined as a prostate‐specific antigen (PSA) doubling time of ≤10 months during continuous ADT.

Coverage in Quebec: RAMQ* List of Exceptional Medications

1. Patient Eligibility:
   • For treatment of nmCRPC in patients at high risk of developing distant metastases despite androgenic deprivation treatment. High risk is defined as a prostate specific antigen (PSA) doubling time ≤10 months; and
   • whose ECOG performance status is 0 or 1.
2. Authorization Duration: maximum duration of each authorization is 4 months.
3. Prescriber Requirements: when requesting continuation of treatment, the physician must provide evidence of a beneficial clinical effect defined by the absence of disease progression.

*Official mark of the Régie de l'assurance maladie du Québec (RAMQ).

1. Patient Eligibility: for the treatment of mCSPC, in patients who:
   • Have not received an ADT for more than 6 months for treatment of metastatic prostate cancer.
   • ECOG performance status is 0 or 1.
2. Prescriber Requirement & Coverage Duration:
   • New eligible mCSPC patients initiating NUBEQA + ADT may be submitted directly to RAMQ for public coverage. Maximum duration of initial authorization is 6 months.
   • Subsequent authorizations are authorized for up to 12 months if the prescriber provides evidence of a beneficial clinical effect, demonstrated by the absence of disease progression.
3. Clinical Notes:
   • A clinical reassessment by the prescriber is required periodically to ensure that the beneficial clinical effect, defined by the absence of disease progression, is maintained. Otherwise, treatment must be discontinued.
   • Darolutamide is NOT authorized following the failure of an androgen synthesis inhibitor or a second-generation androgen receptor inhibitor if these agents were administered to treat prostate cancer.

1. Reimbursement criteria: In combination with docetaxel and androgen deprivation therapy (ADT) for the treatment of metastatic castration-sensitive prostate cancer in people:
   • who have not received ADT for more than 6 months for the treatment of metastatic prostate cancer; and
   • whose ECOG performance status is 0 or 1.
2. Prescriber requirement: A request for coverage may be submitted to the public plan for new patients with mCSPC who have been prescribed NUBEQA in combination with docetaxel.
3. Renewals and authorization duration:
   • Maximum duration of initial authorization is 4 months.
   • When requesting continuation of treatment, the physician must provide evidence of a beneficial clinical effect defined by the absence of disease progression.
4. Exclusion criteria: It should be noted that darolutamide is not authorized following the failure of an androgen synthesis inhibitor or a second-generation androgen receptor inhibitor, if administered for the treatment of prostate cancer.
5. Indication recognized on formularies:
   • For the continuation of treatment of metastatic castration-sensitive prostate cancer in people who have received a treatment combining darolutamide, androgenic deprivation therapy and docetaxel in a hospital setting for 6 cycles of 21 days or whose Docetaxel had to be discontinued due to serious intolerance.

Coverage in Saskatchewan: Special Status

1.  Eligibility Requirements: nmCRPC in combination with ADT in patients who:
   • Have histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features.
   • Have no detectable distant metastases by either CT, MRI, or technetium-99 bone scan, including any central nervous system, vertebral, or meningeal involvement, but excluding pelvic lymph nodes <2cm in short axis (N1) located below the common iliac vessels.
   • Are at high risk of developing metastases (PSADT of ≤10 months during continuous ADT).
   • (If applicable) have demonstrated a further rise in PSA, measured at least 6 weeks after discontinuing treatment with a first-generation anti-androgen (e.g., bicalutamide).
2. Medical Notes:
   • Castration-resistant prostate cancer is defined as three consecutive rises in PSA, measured at least 1 week apart, with the last PSA >2 mcg/L, during continuous ADT with castrate testosterone levels (<1.7 nmol/L).
3. Funding Notes:
   • If biochemical progression (rising PSA) occurs while on darolutamide, appropriate clinical evaluation and/or investigations for metastatic disease should be conducted in a timely manner.
   • If progression to mCRPC occurs during darolutamide treatment for nmCRPC, abiraterone is funded as a treatment option.
   • If darolutamide was discontinued in the nmCRPC setting (i.e., patient choice, intolerance) prior to the development of metastatic disease, either abiraterone or enzalutamide is funded as an option for treatment at the time of progression to mCRPC.

1. Patient Eligibility:
   • Metastatic castration‑sensitive prostate cancer (i.e., positive bone scan, metastatic lesions on radiologic imaging for soft tissue; patients with disease limited to regional pelvic lymph nodes only are not eligible) is treated in combination with ADT.
   • Had no prior ADT in the metastatic setting,
     or
     ADT was initiated within 6 months in the metastatic setting with no disease progression.
2. Prescriber requirements: submit reimbursement request directly to Saskatchewan Cancer Agency.
3. Funding Notes:
   • Darolutamide is funded in patients who previously received adjuvant androgen deprivation therapy (ADT) in the non-metastatic setting as long as ADT was completed >1 year prior to initiation of darolutamide.
   • Darolutamide is funded in patients who received recent docetaxel chemotherapy for the treatment of mCSPC within the past three months if they have not experienced disease progression.
   • Patients unable to tolerate darolutamide may be transitioned to either apalutamide, enzalutamide, or abiraterone plus prednisone for treatment of mCSPC is there is no disease progression.
   • Patients who experience disease progression on darolutamide for treatment of mCSPC are eligible for abiraterone plus prednisone for treatment of mCRPC if they are unable to tolerate or are not candidates for other therapeutic choices (i.e., chemotherapy) provided they have previously not experienced disease progression on abiraterone in any setting.

1. Patient Eligibility:
   • mCSPC treated with darolutamide in combination with docetaxel and ADT in previously untreated patients.
2. Prescriber Requirements:
   • For eligible new mCSPC patients initiating NUBEQA in combination with docetaxel, submissions may be made directly to the Saskatchewan Formulary.
3. Funding Notes:
   • Darolutamide is not funded in patients who have received prior treatment with androgen receptor axis-targeted (ARAT) therapy (i.e., abiraterone, apalutamide, enzalutamide), chemotherapy, or immunotherapy for prostate cancer.
   • Darolutamide is not funded in patients who received androgen deprivation therapy (ADT) in the metastatic setting for more than 6 months, or if it has been less than 1 year since completing adjuvant ADT in the non-metastatic setting.
   • Darolutamide is also funded in patients with only regional lymph node metastases.
   • Patients who are unable to tolerate docetaxel may continue with darolutamide and ADT.