Xtandi

Enzalutamide

• Brand(s): Xtandi
• Dosage Form/Strength: 40 mg capsule
• Updated: December 1, 2021

Initiation criteria for metastatic castration sensitive prostate cancer (mCSPC):

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

1. Enzalutamide is used in combination with androgen deprivation therapy (ADT)¹; AND

2. Metastatic lesions detected on technetium-99m bone scan, computed tomography (CT), and/or magnetic resonance imaging (MRI); 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 enzalutamide OR ADT used in the neoadjuvant or adjuvant setting where the patient has been off treatment for 12 months or more prior to start of enzalutamide; AND

4. Has not experienced disease progression with another an androgen receptor axis targeted therapy (ARAT) for castration sensitive prostate cancer; AND

5. Patient has good performance status.

¹ADT is not required for patients with bilateral orchiectomy

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:

• Number of metastatic lesions on bone scan and in soft tissues
• Testosterone level
• Baseline (pre-treatment) PSA level
• Pre-treatment Gleason score (optional)

Notes:

1. Patients who have previously progressed on a second-generation androgen receptor inhibitor (e.g., apalutamide, enzalutamide, darolutamide) for prostate cancer will not be eligible for enzalutamide in mCSPC. The Ministry will fund only one of enzalutamide or apalutamide in patients with mCSPC.

2. Patients treated with apalutamide or darolutamide as part of a clinical trial may be eligible for enzalutamide and will be considered on a case-by-case basis.

3. Patients who progress on treatment with enzalutamide or apalutamide mCSPC will not be eligible for enzalutamide in the metastatic castration resistant setting.

4. Patients who are currently on a treatment regimen with an androgen receptor axis targeted therapy (e.g., abiraterone or a second-generation androgen receptor inhibitor) for prostate cancer, must meet the initiation criteria if they wish to switch to publicly funded enzalutamide for mCSPC.

5. Time limited funding consideration will be provided on a case-by-case basis for 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: 160 mg administered orally once daily.

Renewal Criteria:
Renewals will be considered in patients until disease progression (i.e., PSA elevation in addition to radiographic disease progression, or PSA progression in addition to clinical symptoms associated with cancer progression), development of castration resistant disease, or experiencing unacceptable toxicity while on enzalutamide.

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

• Patients who have previously experienced disease progression on enzalutamide or another ARI used in the setting of prostate cancer.
• Patients who have risk factors for seizures
• Enzalutamide will not be funded as combination therapy with another androgen receptor axis targeted therapy.

Approved Dosage for Initials and Renewals: 160 mg administered orally once daily.

Duration of initial and renewal approvals: 1 year

Initiation Criteria for high-risk non-metastatic castration resistant prostate cancer (nmCRPC):

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

1. Patient using Xtandi 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 castration 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;
   
   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.

Approval Duration: 1 year

Exclusion Criteria:

• The patient received prior chemotherapy for the treatment of prostate cancer, unless it was in the adjuvant or neoadjuvant setting.
• The patient has previously experienced disease progression on apalutamide or darolutamide used for prostate cancer.
• The patient has risk factors for seizures.

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)

Approved Dosage: 160mg administered orally once daily

Notes:

1. The Ministry will fund only one second generation androgen receptor inhibitor (e.g., apalutamide, darolutamide, or enzalutamide) in patients with nmCRPC.

2. Patients who have progressed on enzalutamide in nmCRPC will not be eligible for enzalutamide in metastatic castration resistant prostate cancer (mCRPC).

3. Requests for enzalutamide in patients who have initiated another ARI therapy in the nmCRPC setting and who have not experienced disease progression will be considered on a case-by-case basis.

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

Approval Duration: 1 year

Initiation criteria for metastatic castration resistant prostate cancer (mCRPC):

For the treatment of metastatic castration resistant prostate cancer (mCRPC) in patients meeting the following criteria:

1. Enzalutamide is used in combination with androgen deprivation therapy (ADT)¹; AND

2. Metastatic lesions detected on a bone scan, computed tomography (CT), and/or magnetic resonance imaging (MRI); AND

3. Patient has castration resistant disease based on meeting the following indicia observed while on continuous ADT treatment or post orchiectomy:

4. Castrate serum testosterone levels; AND

5. Biochemical progression defined as three (3) prostate-specific antigen (PSA) rises at least 1 week apart, with the last PSA greater than 2ng/mL AND/OR radiographic progression of new or pre-existing disease as determined by the detection of 2 or more lesions on bone scan or presence of new soft tissue lesions by RECIST criteria; AND

6. Patient has progressed on a docetaxel-based chemotherapy
   OR
   Patient is using enzalutamide pre-docetaxel for metastatic castration resistant prostate cancer and has not previously experienced disease progression on enzalutamide or another second-generation androgen receptor inhibitor (e.g., apalutamide, darolutamide,) used for prostate cancer
   OR
   Patient is using enzalutamide pre-docetaxel for mCRPC and has not previously experienced disease progression on abiraterone used in mCRPC sequenced immediately prior to enzalutamide;

   AND

7. Patient has good performance status defined as an Eastern Cooperative Oncology Group (ECOG) Performance status less than or equal to 2.

¹ADT is not required for patients with bilateral orchiectomy

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)

Notes:

1. Patients who have progressed on treatment with second generation androgen receptor inhibitors (e.g., apalutamide, enzalutamide, darolutamide) used in prior stages of prostate cancer will not be eligible for enzalutamide in the metastatic castration resistant setting.

2. Patients treated with apalutamide or darolutamide as part of a clinical trial may be eligible for enzalutamide and will be considered on a case-by-case basis.

3. Requests for enzalutamide in patients who initiated abiraterone therapy and who have not had disease progression while on abiraterone will be considered on a case-by-case basis.

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

• The patient has risk factors for seizures;
• Enzalutamide will not be funded as combination therapy with another androgen receptor axis targeted therapy or cabazitaxel.

Renewals:
Renewals will be considered in patients who have not experienced disease progression while on enzalutamide therapy.

Approved Dosage for Initials and Renewals: 160 mg administered orally once daily.

Duration of initial and renewal approvals: 1 year

EAP Drug Request Form:

Standard Form for EAP Drug Requests