LYNPARZA (olaparib)

LynparzaTM (olaparib) is a first‐in‐class PARP inhibitor (PARPi) that allows women with BRCA mutated (BRCAm) platinum‐sensitive relapsed high-grade serous ovarian cancer to extend progression‐free survival (PFS).1-3

Prescribing Information

Indications and Usage

LynparzaTM (olaparib) is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCAm high-grade serous ovarian cancer (including fallopian tube or primary peritoneal) who are in response (complete response or partial response) to platinum-based chemotherapy.4

Lynparza is recommended by NICE within its marketing authorisation for patients only if:

  • They have had 3 or more courses of platinum based chemotherapy and
  • The drug cost of Lynparza for people who remain on treatment after 15 months will be met by AstraZeneca.5

Lynparza is recommended by the SMC in line with its marketing authorisation.6

Dosing and Administration

Lynparza is the only approved oral maintenance therapy for BRCAm platinum-sensitive relapsed high-grade serous ovarian cancer patients.4 

The recommended dose of Lynparza is 400 mg (eight 50 mg capsules) taken twice daily, equivalent to a total daily dose of 800 mg.4

Image showing how to take Lynparza 400mg around morning and evening mealtimes
Image showing how to take Lynparza 400mg around morning and evening mealtimes

Dose Adjustments

Dose adjustments and/or dose interruptions may be required to manage adverse events such as nausea, vomiting, diarrhoea and anaemia4. Refer to SmPC for more information and specific recommendations.

Dose adjustments with Lynparza
Dose adjustments with Lynparza
Image showing recommended dose reduction from 400mg to 200mg to 100mg as a final reduction
Image showing recommended dose reduction from 400mg to 200mg to 100mg as a final reduction

Safety and Tolerability

The safety and tolerability of Lynparza are acceptable for oral maintenance treatment administration.4

The most common adverse events associated with Lynparza monotherapy for patients identified with BRCAm were nausea, fatigue and vomiting and were generally mild to moderate (grade 1 or 2) in severity. The most common Grade 3 and 4 adverse events reported for Lynparza vs placebo in the BRCAm population were fatigue (7% vs 2%) and anaemia (5% vs 2%), neutropenia (4% vs 2%) and vomiting (3% vs 0%).3,4

Table showing most common adverse events associated with Lynparza monotherapy for patients identified with BRCAm
Table showing most common adverse events associated with Lynparza monotherapy for patients identified with BRCAm

Warnings and Precautions

Contraindications

  • Hypersensitivity to the active substance or to any of the excipients listed in SmPC.
  • Breast-feeding during treatment and 1 month after the last dose.

Special warnings and precautions for use:

Haematological toxicity has been reported in patients treated with Lynparza. Patients should not start treatment with Lynparza until they have recovered from haematological toxicity caused by previous anticancer therapy.4

  • Baseline testing, followed by monthly monitoring, of complete blood counts is recommended for the first 12 months of treatment and periodically after this time to monitor for clinically significant changes in any parameter during treatment.
  • If a patient develops severe haematological toxicity or blood transfusion dependence, treatment with Lynparza should be interrupted and appropriate haematological testing should be initiated. If the blood parameters remain clinically abnormal after 4 weeks of Lynparza dose interruption, bone marrow analysis and/or blood cytogenetic analysis are recommended.4

Myelodysplastic syndrome/Acute Myeloid Leukaemia (MDS/AML) have been reported in a small number of patients who received Lynparza alone or in combination with other anticancer drugs; the majority of cases have been fatal.4

  • If MDS and/or AML are confirmed while on treatment with Lynparza, it is recommended that the patient be treated appropriately. If additional anticancer therapy is recommended, Lynparza should be discontinued and not given in combination with other anticancer therapy.4

Pneumonitis has been reported in a small number of patients receiving Lynparza, and some reports have been fatal.4

  • If patients present with new or worsening respiratory symptoms such as dyspnoea, cough and fever, or a radiological abnormality occurs, Lynparza treatment should be interrupted and prompt investigation initiated. If pneumonitis is confirmed, Lynparza treatment should be discontinued and the patient treated appropriately.4

Based on its mechanism of action (PARP inhibition), Lynparza could cause foetal harm when administered to a pregnant woman.4

Lynparza should not be used during pregnancy and in women of childbearing potential not using reliable contraception during therapy and for 1 month after receiving the last dose of Lynparza (see section 4.6 of Summary of Product Characteristics).4

Lynparza co-administration with strong CYP3A inducers or inhibitors should be avoided.4 If co-administration with a strong or moderate CYP3A inhibitor must occur, the dose of Lynparza must be reduced. Co-administration with CYP3A inducers may substantially reduce Lynparza efficacy. It is also not recommended to consume grapefruit juice while on olaparib therapy. P-gp inhibitors may increase exposure to olaparib.4

For full dosing and safety information, please click here to see the Summary of Product Characteristics.4

Unmet need in ovarian cancer

Image of the disease course of a patient with late stage ovarian cancer – showing the decreasing PFS times with multiple lines of chemotherapy.
Image of the disease course of a patient with late stage ovarian cancer – showing the decreasing PFS times with multiple lines of chemotherapy.

CA-125 depicted for illustrative purposes only

Patient eligibility for Lynparza

Patients are eligible for treatment with Lynparza only if they have a confirmed BRCA mutation (can be germline or somatic).4

  • Testing for a BRCA mutation at diagnosis could help provide a timely informed decision on the most appropriate treatment strategy for women with ovarian cancer.
  • All cancer patients with a ≥10% probability of having a BRCAm should be offered genetic testing.15,16 All women with high-grade serous ovarian cancer and Grade 3 endometrioid are therefore eligible for testing.17
  • Those who have a confirmed BRCAm status are eligible for maintenance treatment with Lynparza within the licenced indication.4

EMA licence criteria for Lynparza

Image showing marketing authorisation criteria for Lynparza
Image showing marketing authorisation criteria for Lynparza

Lynparza is indicated as a monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy.4

This means that patients can receive Lynparza as a maintenance treatment after their first or any subsequent relapse (i.e. as a second line or beyond maintenance therapy) provided they meet the other eligibility criteria.

NICE reimbursement criteria for Lynparza

Lynparza is recommended by NICE within its marketing authorisation for patients only if:

  • They have had 3 or more courses of platinum based chemotherapy and
  • The drug cost of Lynparza for people who remain on treatment after 15 months will be met by AstraZeneca.5
Image showing NICE criteria for Lynparza
Image showing NICE criteria for Lynparza

SMC criteria for Lynparza

Image showing marketing authorisation criteria for Lynparza
Image showing marketing authorisation criteria for Lynparza

Lynparza is recommended by the SMC in line with its marketing authorisation (i.e. for patients who have had two or more courses of platinum based chemotherapy)6

Patient Profile

This could affect any woman.

Who should be tested for a BRCA mutation?

Early identification of BRCAm status in women diagnosed with ovarian cancer can help identify those who could benefit from risk-reduction strategies18 and inform family members of their increased risk.19

Icon of an older woman
Icon of an older woman

Margaret

Age: 72

Family history: Ovarian cancer

BRCAm are not confined to women who present with ovarian cancer at an earlier age; in fact, over 70% of women with BRCAm are 50 years of age or older at diagnosis.19 ESMO guidelines recommend testing all high-grade serous patients with ovarian cancer for BRCAm status regardless of family history or age.20 NICE recommend all women with a ≥10% chance of having a BRCA gene mutation should be tested;15 BGCS guidelines class all women with high-grade ovarian cancer as having a 10% chance of having a BRCA gene mutation.17

Icon of a woman
Icon of a woman

Valerie

Age: 50

Family history: None

Data suggests that approximately 40% of patients with BRCA-mutated ovarian cancer may have no documented relevant family history.21, 22 Guidelines are evolving to recommend BRCAm testing in all women with high-grade serous ovarian cancer in recognition that many more may have BRCAm beyond those diagnosed at an early age or those with a family history. 15-17, 20

Icon of a young woman
Icon of a young woman

Rachael

Age: 37

Family history: Breast and ovarian cancer

While only 0.1–0.3% of the general population are estimated to carry BRCAm,23-26 approximately 15% of women with ovarian cancer have germline BRCAm, with an even higher prevalence in women with high-grade serous ovarian cancer.22 Restricting genetic testing to patients diagnosed at a young age or those with a family history means that many women with BRCAm may be missed.27