Reimbursement Recommendation

Olaparib

Reimbursement request: For the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated, HER2-negative, unresectable locally advanced or metastatic breast cancer who have been previously treated with chemotherapy

Requester: Public drug programs

Recommendation: Reimburse with conditions

What Is the Reimbursement Recommendation for Olaparib?

The Formulary Management Expert Committee (FMEC) recommends that olaparib be reimbursed for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated, HER2-negative, unresectable locally advanced or metastatic breast cancer who have been previously treated with chemotherapy, provided certain conditions are met.

What Are the Conditions for Reimbursement?

Olaparib may be initiated for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated, HER2-negative, unresectable locally advanced or metastatic breast cancer who have been previously treated with chemotherapy. Olaparib should be discontinued if there is disease progression or unacceptable toxicities. The initial prescribing should be limited to medical oncologists with expertise in the management and diagnosis of breast cancer. A price reduction for olaparib may be required.

Why Did Canada’s Drug Agency Make This Recommendation?

FMEC reviewed 1 phase III randomized controlled trial, 2 phase II single-arm cohort studies, and a cost comparison of olaparib versus other treatments used in Canada. Evidence from the randomized controlled trial showed that olaparib provides a clinically meaningful delay in disease progression, no effect on overall survival, and uncertain effects on objective response rate and health-related quality of life (HRQoL) in patients with germline BRCA-mutated metastatic breast cancer. The overall incidence of adverse events was similar between olaparib and chemotherapy, although the adverse event profiles differed. The evidence in patients with somatic BRCA-mutated metastatic breast cancer is very uncertain.

FMEC concluded that there is a significant clinical need arising from BRCA-mutated, HER2-negative, unresectable locally advanced or metastatic breast cancer. FMEC concluded that olaparib for patients with germline BRCA1 or BRCA2 mutations demonstrates acceptable clinical value versus appropriate comparators in the setting in Canada. FMEC also concluded that it is uncertain whether olaparib for patients with somatic BRCA1 or BRCA2 mutations demonstrates acceptable clinical value versus appropriate comparators in the setting in Canada. Olaparib would potentially address significant nonclinical needs (e.g., treatment burden, travel requirements, impact on family, out-of-pocket costs, access inequities). The recommendation also considered economic considerations and impacts on health systems.

Review Background

What Is HER2-Negative Unresectable Locally Advanced or Metastatic Breast Cancer With Deleterious or Suspected Deleterious BRCA Mutations?

HER2-negative unresectable locally advanced or metastatic breast cancer with deleterious or suspected deleterious BRCA mutations is characterized by substantial symptom burden, reduced HRQoL, and poor prognosis. The disease is generally considered incurable, with 5-year net survival estimates of 74% for unresectable locally advanced disease and 23.2% for metastatic disease. At diagnosis, 12.4% of patients have unresectable locally advanced disease, and 4.9% have metastatic breast cancer. Germline BRCA1 or BRCA2 pathogenic variants are identified in approximately 5% to 10% of patients with breast cancer, whereas somatic BRCA1 or BRCA2 mutations are less common, occurring in approximately 3% of cases.

What Are the Current Treatment Options?

Current treatment options for metastatic breast cancer in Canada are guided by tumour subtype. Hormone receptor (HR)-positive disease is typically treated with a CDK4/6 inhibitor in combination with endocrine therapy, with the potential addition of a PIK3CA-targeted agent for eligible patients, followed by antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan or sacituzumab govitecan and subsequent chemotherapy. Triple-negative breast cancer (TNBC) is typically treated with chemotherapy with or without pembrolizumab, followed by ADCs and later-line chemotherapy. Clinical experts noted limited emerging evidence supporting poly-(ADP-ribose) polymerase (PARP) inhibitors in tumours with somatic BRCA mutations. Other emerging first-line treatment options for PD-L1–positive disease include datopotamab deruxtecan and sacituzumab govitecan.

What Is the Treatment Under Review?

Olaparib is a targeted PARP inhibitor administered orally at a dose of 300 mg (two 150 mg tablets) twice daily until disease progression or unacceptable toxicity. Health Canada has approved olaparib as monotherapy for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated, HER2-negative metastatic breast cancer who have been previously treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with HR-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy.

The reimbursement-requested indication is broader than the Health Canada–approved indication. Specifically, whereas the Health Canada indication is limited to patients with germline BRCA-mutated metastatic breast cancer, the reimbursement request expands the eligible population to include patients with unresectable locally advanced or metastatic disease who have either germline or somatic BRCA mutations.

Why Did We Conduct This Review?

At the request of the participating public drug programs, Canada’s Drug Agency (CDA-AMC) reviewed the available evidence for olaparib to inform a recommendation on whether it should be reimbursed for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated, HER2-negative, unresectable locally advanced or metastatic breast cancer who have been previously treated with chemotherapy. The data protection for olaparib has expired, so this drug is eligible for a nonsponsored reimbursement review, per the Procedures for Reimbursement Reviews. At the time of this review, 3 generic olaparib submissions are under review by Health Canada.

Summary of Input from Interested Parties

• Three patient groups, Breast Cancer Canada, Canadian Breast Cancer Network, and Rethink Breast Cancer, took part in a CDA-AMC-led facilitated discussion.

• One patient group, Breast Cancer Canada, also provided written input and emphasized the need for treatments that delay disease progression, prolong survival, and maintain HRQoL, while highlighting the limitations of current therapies, including inadequate disease control and significant side effects that impact daily functioning, and the need for more effective, better-tolerated, and convenient oral treatment options and targeted therapies, multiple lines of therapy, and choice of treatment.

• Two clinician groups, Ontario Health (Cancer Care Ontario’s) Breast Cancer Drug Advisory Committee and Research Excellence, Active Leadership (REAL) Canadian Breast Cancer Alliance, indicated that treatment goals in metastatic breast cancer are to delay disease progression, prolong survival, control symptoms, minimize toxicity, and maintain HRQoL; however, significant unmet needs remain, including the incurable nature of the disease, chemotherapy burden, limited access to targeted oral therapies, lack of publicly funded targeted options for germline BRCA-mutated disease, and delays in BRCA testing.

• Public drug plans inquired about the evidence for olaparib to inform a recommendation about whether it should be reimbursed for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated, HER2-negative, unresectable locally advanced or metastatic breast cancer who have been previously treated with chemotherapy. The public drug plans outlined implementation questions related to relevant comparators, initiation of therapy, discontinuation, generalizability, and care provision.

Person With Lived Experience

A person with lived experience from Ontario shared her treatment journey with breast cancer. She was diagnosed with stage II, TNBC in 2018 and had undergone lumpectomy, chemotherapy and radiation therapy. Midway through treatment, she had a double mastectomy, her ovaries and tubes removed, and a total hysterectomy after genetic testing discovered she carried the BRCA1 mutation. Given the aggressive nature of TNBC and the limited treatment options available, she joined the Olympia trial. As a young mother of 4 daughters, survival was the only outcome she cared about. Although she is not sure if she received olaparib or placebo, she suspects she received olaparib due to the nausea and fatigue she experienced the first few months of the trial. She noted that taking the oral pill was convenient as opposed to in-clinic treatments. Compared to chemotherapy and radiation, the side effects were minimal. She was frustrated with the genetic testing process due to delayed referral and the time to receive the results — barriers she experienced due to where she lived. Earlier discovery of the BRCA mutation would have saved her from the lumpectomy that was initially recommended. The delay also disrupted her treatment plan. She reflected on her mother’s diagnosis with stage II, estrogen receptor-positive breast cancer, for which she was referred for testing and received the results within 2 weeks (in Toronto). She took a leave from work after her diagnosis and has yet to return. Following treatment, she was diagnosed with mild cognitive impairment, which was attributed to chemotherapy and the loss of estrogen. Her biggest hope is that there will be treatment options available to her daughters that do not derail their lives.

Disclaimer: The perspectives shared by people with lived experiences who present to the committee reflect their individual experiences and are not necessarily representative of all people with the same condition or course of treatment. Their insights provide valuable context about what a patient, support person, or caregiver might go through when facing this condition or treatment, helping to inform the committee’s deliberations. These narratives complement other forms of evidence and input and should be considered as part of a broader understanding of the condition and treatment under review. When gender or gendered pronouns are used in these narratives, they are included with the permission of the individual.

Recommendation

With a vote of 9 to 0, FMEC recommends that olaparib, for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated, HER2-negative, unresectable locally advanced or metastatic breast cancer who have been previously treated with chemotherapy, be reimbursed if the conditions presented in Table 1 are met.

Table 1: Conditions, Reasons, and Guidance

CDA-AMC = Canada’s Drug Agency; FMEC = Formulary Management Expert Committee; HR = hormone receptor.

Summary of Deliberation

FMEC deliberated on all domains of value of the deliberative framework before developing its recommendation: clinical value, unmet clinical need, distinct social and ethical considerations, economic considerations, and impacts on health systems. For further information on the domains of value, please refer to the Expert Committee Deliberation at Canada’s Drug Agency document.

FMEC considered the following key discussion points, organized by the 5 domains of value.

Clinical Value

• FMEC concluded that olaparib for patients with germline BRCA1 or BRCA2 mutations demonstrates acceptable clinical value versus appropriate comparators in Canada.

• FMEC concluded that it is uncertain whether olaparib for patients with somatic BRCA1 or BRCA2 mutations demonstrates acceptable clinical value versus appropriate comparators in Canada.

• Through reflection on the input from patient groups and insight shared by a person with lived experience, FMEC members noted that patients value access to targeted therapies that are associated with fewer or more manageable side effects, reduced clinic time, and less impact on quality of life.

• FMEC members highlighted the following discussion points:

  • Appropriate comparators. The committee agreed that the comparators in the phase III OlympiAD trial (treatment of physician’s choice [TPC]: capecitabine, eribulin, or vinorelbine) were appropriate at the time the study was conducted. However, current standards of care have evolved. More relevant comparators now include pembrolizumab in combination with chemotherapy for PD-L1-positive TNBC; trastuzumab deruxtecan for HR-positive, HER2-low disease; and sacituzumab govitecan for patients with TNBC or HR-positive disease.

  • Outcomes assessed. The committee agreed that patients with locally advanced unresectable or metastatic breast cancer value treatments that extend survival, preserve HRQoL, and maximize time without chemotherapy or its associated toxicities.

  • Efficacy. FMEC noted that the OlympiAD trial demonstrated a clinically meaningful improvement in progression-free survival (PFS) with olaparib compared to TPC (median 7.0 months versus 4.2 months; hazard ratio = 0.58; 95% confidence interval, 0.42 to 0.8; P < 0.001) in patients with germline BRCA1 or BRCA2 mutations. There was no clinically meaningful or statistically significant difference between groups in overall survival (19.3 months versus 17.1 months).

  • The committee also reviewed the phase II TBCRC 048 study and its expansion cohort, which evaluated olaparib in patients with somatic BRCA1 or BRCA2 mutations. These single-arm, noncomparative studies demonstrated clinical activity in both subgroups, with objective response rates and PFS that were broadly consistent with those observed in patients with germline BRCA1 or BRCA2 mutations. In the expansion cohort, median PFS was 5.5 months in the somatic BRCA1 or BRCA2 subgroup.

  • The committee also noted that no studies have directly compared olaparib with current standards of care, including pembrolizumab-based therapy or ADCs, in the metastatic setting.

  • Harms. The committee noted that important long-term harms of olaparib include myelodysplastic syndrome and acute myeloid leukemia, which were not observed in the trials reviewed. Common short-term adverse events include anemia, nausea, vomiting, and fatigue; FMEC learned from the person with lived experience and input from interested parties that these harms are manageable. Adverse events of chemotherapy vary by regimen but commonly include neutropenia, febrile neutropenia, gastrointestinal toxicity, fatigue, peripheral neuropathy, and hand-foot syndrome. While some toxicities overlap between olaparib and chemotherapy, they are generally manageable through dose interruptions or dose reductions.

  • Level of certainty in clinical value. The committee agreed that there is an acceptable level of certainty in clinical value for olaparib in patients with germline BRCA1 or BRCA2 mutations compared to TPC based on the OlympiAD trial. However, the evidence supporting use in patients with somatic BRCA1 or BRCA2 is derived from small, noncomparative studies and is therefore associated with greater uncertainty.

  • FMEC heard agreement from the guest specialist that there are no data for locally advanced, unresectable disease, although in clinical practice it is treated in a similar manner to metastatic disease. Because treatment is typically palliative rather than curative, many patients prefer to avoid highly aggressive therapies, making olaparib an appropriate treatment option.

  • The committee agreed that patients with somatic BRCA1 or BRCA2 mutations should be eligible for olaparib with the same conditions as those with germline BRCA1 or BRCA2 mutations. The specialist noted that these cancers evolve as they progress and metastasize, and that BRCA1 or BRCA2 alterations can represent an important biological driver of tumour behaviour and treatment sensitivity.

Unmet Clinical Need

• FMEC concluded that there is a significant clinical need arising from BRCA-mutated, HER2-negative, unresectable locally advanced or metastatic breast cancer.

• Through reflection on the input from patient groups or insights shared by the person with lived experience, FMEC members noted that patients have an ongoing need for timely access to personalized therapies that improve survival while maintaining quality of life. Limited access to precision oncology delays the use of optimal therapies and often results in earlier use of chemotherapy, which many patients wish to postpone because of its toxicity and impact on quality of life.

• FMEC members highlighted the following discussion points:

  • Availability of treatment options. FMEC agreed that alternative treatments are effective and generally well tolerated. The TPCs are older, established therapies with well-characterized safety profiles that clinicians have extensive experience managing. Newer therapies, including immunotherapies and ADCs, are associated with distinct toxicities in addition to those commonly seen with chemotherapy.

  • Compared with these newer therapies, olaparib has a more manageable safety profile and is administered orally, avoiding the need for IV access, regular infusions, and frequent visits to chemotherapy clinics.

  • Severity of the disease. The committee agreed that locally advanced unresectable and metastatic breast cancer is an incurable condition associated with ongoing disease burden. The intent of all therapies is viewed as palliative.

  • Significant unmet clinical need. The committee recognized that patients would value targeted oral therapy that prolongs life, improves HRQoL and PFS, and delays the need for chemotherapy.

  • Olaparib addresses the unmet clinical need of improving PFS as an oral targeted therapy. Compared with chemotherapy, olaparib is associated with fewer and more manageable adverse events, which is expected to improve HRQoL. Patients want choice of multiple lines of therapy because the progressive nature of the disease means options diminish over time.

  • Evidence generation. The committee acknowledged that germline BRCA1 or BRCA2 mutations are identified in approximately 5% to 10% of patients with breast cancer, whereas somatic BRCA1 or BRCA2 mutations occur in approximately 2% to 3% of cases. Based on approximately 30,000 new breast cancer diagnoses annually in Canada, this corresponds to roughly 1,500 to 3,000 patients with germline BRCA1 or BRCA2 mutations and 600 to 900 patients with somatic BRCA1 or BRCA2 mutations each year. Phase III trials for these molecular subgroups require multinational, multi-institutional collaboration and have historically taken years to complete, even for patient populations with the more common germline BRCA1 or BRCA2 mutation. The substantially lower prevalence of somatic BRCA1 or BRCA2 mutations makes generation of robust phase III evidence even more challenging.

  • The committee heard from the guest specialist that having more treatment options is important in metastatic breast cancer, for which care is long-term rather than a short-term intervention. Olaparib may provide an opportunity for patients to have a treatment option that avoids or delays exposure to therapies associated with cumulative toxicities, such as neuropathy, which is particularly relevant for patients with pre-existing neuropathy.

Distinct Social and Ethical Considerations

• FMEC concluded that there is a significant nonclinical need arising from BRCA-mutated, HER2-negative, unresectable locally advanced or metastatic breast cancer.

• FMEC did not identify any important measures that should be implemented to ensure that the use of olaparib addresses relevant social and ethical implications.

• Through reflection on the input from patient groups or insights shared by people with lived experience, FMEC members noted that BRCA-mutated breast cancer is often diagnosed in younger adults during their peak working and caregiving years. As a result, the disease and its treatment can significantly disrupt employment, finances, family responsibilities, fertility, and family planning.

• FMEC members highlighted the following discussion points:

  • Unmet nonclinical needs. The committee agreed that an oral therapy such as olaparib would be less burdensome for patients and their families, given that it requires less travel to the hospital and to clinics, does not require prolonged IV access, and would address inequitable access to funding for oral cancer drugs.

  • Olaparib is an oral therapy, whereas capecitabine was the only oral option among the chemotherapy comparators evaluated. Patient groups indicated a preference for oral therapies because of their greater convenience and reduced treatment burden.

  • Social and ethical considerations. FMEC heard from the guest specialist that education and awareness of the expanded eligibility criteria for publicly funded genomic testing will be important to ensure appropriate implementation. Access to germline BRCA testing may be limited by restrictive eligibility criteria, lack of awareness of testing indications, delays in testing and result reporting, and out-of-pocket costs for patients who do not qualify for publicly funded testing.

  • FMEC noted that germline BRCA mutations are more commonly identified in younger patients and in certain populations with a higher prevalence of founder mutations, including individuals of Ashkenazi Jewish, Icelandic, and French-Canadian ancestry. Improving access to education, appropriate risk assessment, and timely genetic counselling and testing is essential to identify eligible patients. Patients with a tumour found to harbour a somatic BRCA mutation should also be referred for germline genetic testing, as recommended by current clinical practice.

  • FMEC agreed that somatic mutations should be routinely tested across the country for metastatic breast cancer.

Economic Considerations

• FMEC concluded that there are economic considerations that are important to address when implementing olaparib.

• FMEC members highlighted the following discussion points:

  • At publicly available list prices, the per-patient 28-day cycle cost of olaparib exceeds the costs of 10 of the 13 comparator therapies considered within the CDA-AMC analysis. The drug costs of olaparib fall below the cost of the 3 newer combination therapies used in the TNBC setting.

  • The comparative effectiveness of olaparib versus many single-agent chemotherapy comparators is unknown. There is therefore insufficient evidence to justify a price premium for olaparib over these other comparators.

  • Only 3 of the relevant 13 comparators (i.e., capecitabine, eribulin, or vinorelbine) were included in the clinical evidence. The comparative effectiveness of olaparib versus the remaining relevant comparators is unknown. Given this uncertainty, a price reduction is warranted.

  • Three generic formulations of olaparib are currently under review by Health Canada. If approved, under the pan-Canadian Pharmaceutical Alliance tiered pricing framework, the per-patient 28-day cycle cost of olaparib is expected to decrease, but would still exceed the costs of 7 of the 13 comparator therapies (at their list prices).

Impacts on Health Systems

• FMEC concluded that there are impacts on health systems that are important to address when implementing olaparib.

• FMEC members highlighted the following discussion points:

  • Impacts on health systems. FMEC agreed that, as an oral therapy, olaparib may reduce demand for cancer clinic and chemotherapy unit resources. However, its implementation would increase demand for genetic counselling and germline testing services, as well as pathology resources for next-generation sequencing to identify eligible patients with somatic BRCA mutations.

  • The committee noted that funding for oral anticancer therapies remains inconsistent across Canada, which may create inequities in access, particularly for younger patients who may not have comprehensive provincial or private drug coverage.

  • Considerations for health system sustainability. The committee agreed that olaparib may delay or reduce the need for IV chemotherapy, thereby decreasing use of chemotherapy unit resources. However, given the relatively small eligible patient population, the overall impact on health system resource utilization is expected to be minimal.

  • Equity implementation. The committee acknowledged that equitable implementation will require timely access to genetic counselling and germline testing for BRCA1 or BRCA2 mutations, which are routinely included in multigene panel testing, as well as access to tumour testing to identify somatic BRCA mutations in patients with metastatic or locally advanced unresectable disease. If universal tumour testing is not feasible, clear eligibility criteria or testing algorithms will be needed to identify patients most likely to benefit.

Sources of Information Used by the Committee

To make its recommendation, the committee considered the following information (links to the full documents for the review can be found on the project webpage):

• the CDA-AMC review of the clinical and pharmacoeconomic evidence related to olaparib (refer to the Main Report and the Supplemental Material document)

• patients' perspectives gathered by 3 patient groups, Breast Cancer Canada, Canadian Breast Cancer Network, and Rethink Breast Cancer (refer to the Patient and Clinician Group Input document)

• input from a person with lived experience who delivered a brief presentation and answered questions from the committee (refer to the Person With Lived Experience section earlier in this document)

• input from 2 clinician groups, Ontario Health (Cancer Care Ontario) Breast Cancer Drug Advisory Committee and REAL Canadian Breast Cancer Alliance (refer to the Patient and Clinician Group Input document)

• input from public drug programs that participate in the reimbursement review process (refer to the FMEC Responses to Questions from the Drug Program document)

• input from 2 clinical experts with expertise in the management of breast cancer malignancies consulted by CDA-AMC.

Feedback on Draft Recommendation

CDA-AMC received feedback from 2 clinician groups (the Ontario Health (Cancer Care Ontario) Breast Cancer Drug Advisory Committee and REAL Canadian Breast Cancer Alliance), 2 patient groups (Breast Cancer Canada and Canadian Breast Cancer Network), the drug manufacturer (AstraZeneca Canada), and the public drug programs. All groups generally agreed with the recommendation. The following issues were raised that were outside the scope of the reimbursement review: treatment as front-line without requiring prior chemotherapy, germline PALB2 mutations, and re-treatment.

All feedback received in response to the draft recommendation is available on the CDA-AMC project webpage.

FMEC Information

Members of the Committee

Dr. Emily Reynen (Chair), Dr. Hardit Khuman (Vice-Chair), Dr. Zaina Albalawi, Ms. Marilyn Barrett, Ms. Valerie McDonald, Dr. Bill Semchuk, Dr. Jim Silvius, Dr. Marianne Taylor, Dr. Maureen Trudeau, Dr. Dominika Wranik. Two guest specialists from New Brunswick and Ontario participated in this review.

Regrets: Two clinical experts were consulted for the clinical and pharmacoeconomic report. One clinical expert was unable to attend the meeting as a guest specialist.

Meeting date: July 16, 2026

Conflicts of interest: None

Special thanks: CDA-AMC extends special thanks to Rebecca Dahle who presented directly to FMEC and to the Canadian Breast Cancer Network representing and supporting the community of people living with breast cancer.

Note: CDA-AMC makes every attempt to engage with people with lived experiences as closely to the indication and treatments under review as possible; however, at times, CDA-AMC is unable to do so and instead engages with individuals with similar treatment journeys or experience with comparators under review to ensure lived experience perspectives are included and considered in Reimbursement Reviews. CDA-AMC is fortunate to be able to engage with individuals who are willing to share their treatment journeys with FMEC.