Lynparza

Olaparib

• Brand(s): Lynparza
• Dosage Form/Strength: 100mg tablets, 150mg tablets
• Effective dates: Updated December 23, 2020 (ovarian), May 2, 2022 (prostate), September 15, 2023 (adjuvant breast); November 4, 2024 (Prostate new regimen)

BRCA-mutated, high grade epithelial ovarian, fallopian tube, or primary peritoneal cancer

Initiation Criteria:

For the maintenance treatment of BRCA-mutated, high grade epithelial ovarian, fallopian tube, or primary peritoneal cancer in adult patients who meet ALL the following criteria;

1. Patient has documented mutation in BRCA 1 or BRCA 2 genes (germline or somatic detected by an approved testing method);
   AND
2. Patient is using olaparib as maintenance therapy immediately after one course of first line platinum-based chemotherapy in which radiological response (complete or partial) is demonstrated after at least 4 cycles of treatment;
   OR
   Patient is using olaparib as maintenance therapy in relapsed disease after having received more than one prior course of platinum-based chemotherapy in which platinum sensitive disease¹ was demonstrated with one completed treatment course, and there is radiologic response (complete or partial) to the most recently completed course of platinum-based treatment.²
   AND
3. Olaparib is started within 8 weeks of the patient’s final dose of platinum-based chemotherapy² or within 12 weeks³ with restaging to confirm no disease progression if delay of more than 8 weeks since last dose of chemotherapy has occurred; AND
4. Olaparib is being used as monotherapy for maintenance treatment; AND
5. Patient has good performance status.

¹Platinum-sensitive disease is defined as disease progression/recurrence/relapse occurring at least 6 months following completion of a platinum-based chemotherapy in which an initial response had been demonstrated.

²Patients who are unable to use a platinum-based chemotherapy after having demonstrated platinum- sensitive disease to an earlier line of treatment may be considered on a case-by-case basis if they have received at least 4 cycles of a non-platinum treatment, submit documentation for clinically relevant allergies or intolerance to platinum treatment, and meet all other aspects of the above criteria.

³Patients not able to start olaparib within 12 weeks due to extenuating circumstances may be considered on a case-by-case basis if they have no evidence of disease progression, provide information to explain why treatment could not be started within 12 weeks, and meet all other aspects of the above criteria.

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

• Patients who have relapsed after at least one course of platinum-based chemotherapy and have not demonstrated platinum-sensitive disease¹ will not be funded.
• Patients who have developed disease progression before start of olaparib maintenance therapy will not be funded.
• Retreatment with olaparib as maintenance therapy will not be funded.
• Olaparib is not funded when used as combination with chemotherapy.

Recommended dose: 300 mg twice daily for oral tablets

Approval duration: 1 year

Notes:

1. Imaging to rule out disease progression is required for patients delayed in starting maintenance therapy with olaparib by more than 8 weeks or who have stopped therapy for more than 14 days prior to starting or restarting olaparib (Note: CA-125 clinical assessments may be considered case-by-case where imaging is not available).
2. Cancer antigen 125 (CA-125) and clinical assessments should be done at least every 3 to 4 months to monitor for disease reoccurrence or progression.
3. Olaparib will be funded for a maximum of 2 years in the maintenance setting after first line platinum-based therapy if there is no evidence of disease. Olaparib maintenance therapy will be funded ongoing until disease progression or development of unacceptable toxicity to olaparib for those using in relapsed platinum-sensitive disease.
4. Time limited access to olaparib will be provided for patients already on bevacizumab maintenance who wish to switch to olaparib monotherapy as long as other criteria are met and there is no evidence of disease progression on imaging and within 12 weeks of completing chemotherapy.

Renewal Criteria:

Olaparib maintenance therapy after first line platinum-based treatment.

Ongoing funding will be considered until disease progression or development of unacceptable toxicity or up to a maximum of 2 years if there is no evidence of disease.

Olaparib maintenance therapy in relapsed platinum-sensitive disease:

Ongoing funding will be considered until disease progression or development of unacceptable toxicity

Recommended Dose: 300 mg twice daily for oral tablets

Approval duration of renewals: 1 year
(Note that Olaparib will be funded for a maximum of 2 years in the maintenance setting after first line platinum-based therapy if there is no evidence of disease at 2 years.)

Metastatic castration resistant prostate cancer (mCRPC)

Initiation Criteria:

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

1. Patient is 18 years of age or older;
   AND
2. Provides documentation that patient is positive for deleterious or suspected deleterious germline and/or somatic mutations in the BRCA 1 or BRCA 2 genes¹ using an approved testing method; AND
3. Has metastatic lesions detected on a bone scan, computed tomography (CT), and/or magnetic resonance imaging (MRI)²;
   AND
4. Has castration resistant disease based on meeting the following indicia observed while on continuous androgen deprivation therapy (ADT) treatment or post orchiectomy³:
   o Castrate serum testosterone levels
   AND
   o Biochemical progression defined as three (3) prostate-specific antigen (PSA) rises at least 1 week apart, with the last PSA greater than 2 ng/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
5. Patient is treatment naïve to olaparib or another poly-(ADP-ribose) polymerase (PARP) inhibitor used in the setting of mCRPC;
   AND
6. Patient meets one of the following clinical settings;
   i) Olaparib is used in combination with androgen deprivation therapy (ADT) in a PARP-naive patient who has experienced disease progression on an ARAT/ARPI (e.g., abiraterone, apalutamide, darolutamide, enzalutamide) used at any stage of prostate cancer²;
   OR
   ii) Olaparib is used in combination with abiraterone, and prednisone or prednisolone in a patient who has not used an ARAT/ARPI at any stage of prostate cancer (i.e., treatment naïve to an ARAT/ARPI). If the patient has already initiated a CYP-17 inhibitor (e.g., abiraterone) in mCRPC, they should not have received more than 4 months of treatment with abiraterone prior to initiation of the olaparib;
   AND
7. Patient has good performance status.

Notes:

1. ATM gene mutations can be considered for patients using olaparib as monotherapy anticancer therapy with or without an ADT.
2. Positron emission tomography (PET) imaging results may be considered.
3. ADT is not required for patients with bilateral orchiectomy.

Renewal Criteria:

Renewal of funding will be considered in patients who have not experienced disease progression or unacceptable toxicity while on therapy

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

1. Patients who have previously experienced disease progression on a PARP inhibitor (e.g. olaparib, niraparib) for prostate cancer will not be funded.
2. Combination therapy of olaparib and abiraterone with any of the following in mCRPC will not be funded;
   i) ARI (e.g., enzalutamide)
   ii) Another PARP inhibitor
   iii) Chemotherapy (e.g., docetaxel, cabazitazel)
   iv) Another CYP-17 inhibito

Approval Duration (initials and renewals): 1 year

Approved dose:

Refer to the product monograph for dosing information. Note that the 100 mg tablet can be considered for dose reduction.

Usual standard dose: Olaparib 300 mg twice daily

When used with abiraterone and prednisone: Olaparib 300 mg twice daily with abiraterone, 1000 mg daily and prednisone or prednisolone, 5 mg twice a daily.

Definitions for the purpose of the EAP funding criteria:

• ADT – A first generation androgen deprivation therapy (e.g., goserelin, leuprolide, triptorelin, buserelin, degarelix)
• ARAT – An androgen receptor axis targeted therapy (e.g., abiraterone, apalutamide, darolutamide, enzalutamide). This terminology was used in earlier prostate cancer criteria and is equivalent to ARPI (see below). This is included for clarity and alignment with other ministry criteria.
• ARPI – An androgen receptor pathway inhibitor (e.g., abiraterone, apalutamide, darolutamide, enzalutamide).
• ARI – A second generation androgen receptor inhibitor (e.g., apalutamide, darolutamide, enzalutamide)
• PARP – A Polyadenosine 5-diphosphoribose polymerisation inhibitor (e.g., olaparib, niraparib)
• CYP-17 inhibitor – An inhibitor of cytochrome P450 17α−hydroxy/17,20-lyase (CYP17) enzymes (e.g., abiraterone)

Adjuvant treatment of early breast cancer at high risk of recurrence

Initiation Criteria:

For the adjuvant treatment of adult patients with early breast cancer at high risk of recurrence meeting the following criteria;

1. Patient is 18 years of age or older;
   AND
2. Has documented deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) breast cancer;
   AND
3. Has documented human epidermal growth factor receptor 2 (HER2) - negative breast cancer;
   AND
4. Patient’s eligibility for adjuvant treatment meets one of the following clinicopathological features (Note 1);
   i) Has received surgery followed by adjuvant chemotherapy and diagnosed with triple negative breast cancer (TNBC) with axillary node-positive disease or axillary node-negative disease with a pathological tumour at least 2 cm or larger in size;
   OR
   ii) Has received surgery followed by adjuvant chemotherapy and diagnosed with hormone receptor (HR) positive, HER2-negative breast cancer with at least 4 or more involved pathologically confirmed positive lymph nodes;
   OR
   iii) Has received neoadjuvant chemotherapy followed by surgery and has TNBC with residual invasive breast cancer in the breast and/or resected lymph nodes [i.e. no pathological complete response from neoadjuvant therapy (non-PCR)];
   OR
   iv) Has received neoadjuvant chemotherapy followed by surgery and with HR positive, HER2-negative breast cancer with residual invasive cancer in the breast and/or the resected lymph nodes following neoadjuvant therapy (i.e., non-pCR) and a clinical and pathological stage and estrogen-receptor status and histologic grade (CPS + EG) score equal to 3 or higher (Note 2)
5. Patient must have completed neoadjuvant or adjuvant chemotherapy containing anthracyclines, taxanes, or the combination of both (Note 3);
   AND
6. Olaparib should be initiated at least 2 weeks and no more than 12 weeks following completion of the last treatment, including surgery, chemotherapy, or radiation therapy depending on the situation under which they are eligible. (Note 4)

Exclusion criteria:

1. Patients are not eligible for funding of adjuvant olaparib if they have HER2-positive breast cancer.
2. Patients are not eligible for funding of adjuvant olaparib if they have metastatic breast cancer.
3. Patients who have received both neoadjuvant and adjuvant chemotherapy are not eligible for funding of adjuvant olaparib.

Notes:

1. Please ensure that the request application includes the objective documentation reports for germline BRCA mutations, HER 2 and hormone receptor status, and the pathology reports associated with the clinical eligibility situation.
2. The CPS + EG is a disease scoring system that includes clinical stage, estrogen receptor status, nuclear grade, and post-treatment pathologic stage. Clinicians using alternative risk-assessment tools instead of CPS + EG may be considered case-by-case upon submitting supporting clinical details of the validated alternative risk assessment tool.
3. Patients who are unable to complete at least 6 cycles of neoadjuvant or adjuvant chemotherapy (e.g. due to toxicity) may still be considered for adjuvant olaparib case-by-case if all other eligibility criteria are met.
4. For a time-limited period, patients who missed the 12 week window for initiation of olaparib may be considered case-by-case upon meeting all other eligibility criteria.
5. Renewal of funding will not be considered, however, patients who have experienced treatment interruptions may be considered for restarts on a case-by-case basis for up to a total of 12 months of adjuvant therapy as long as the treatment break was not related to disease recurrence or development of unacceptable toxicities.

Discontinuation criteria:
Olaparib in the adjuvant setting will be funded until the occurrence of any of the following, whichever occurs first:

1. Completion of a total of 1 year (i.e., 52 weeks) of treatment;
   OR
2. Until disease recurrence;
   OR
3. Until development of unacceptable toxicities from treatment with olaparib.

Approval duration of Initials: 52 weeks

Renewals are not considered. (See Note 5)

Recommended dose:

300 mg twice daily. Dose reductions as necessary based on the product monograph.

EAP Drug Request Form:

Standard Form for EAP Drug Requests