LYNPARZA

What it is

LYNPARZA contains olaparib 100 mg or 150 mg and is supplied as film-coated tablets. Olaparib is an orally active inhibitor of human poly(ADP-ribose) polymerase enzymes, including PARP-1, PARP-2, and PARP-3.

Approved indications

— Maintenance treatment of adult patients who have advanced, high-grade, epithelial ovarian, fallopian tube or primary peritoneal cancer with a deleterious or suspected deleterious BRCA mutation (germline or somatic), which is in response (complete or partial) to first-line platinum-based chemotherapy. — Maintenance treatment of adult patients who have platinum-sensitive relapsed, high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer which is in response (complete or partial) after platinum-based chemotherapy, where prior treatment must have included at least 2 courses of platinum-based regimens. — Maintenance treatment of adult patients who have advanced, epithelial ovarian, fallopian tube or primary peritoneal cancer which is in response (complete or partial) to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either a deleterious or suspected deleterious BRCA mutation (germline or somatic), and/or genomic instability, in combination with bevacizumab. — Adjuvant treatment of adult patients who have HER2-negative, high-risk early breast cancer with a deleterious or suspected deleterious germline BRCA mutation (gBRCAm), for which they have previously been treated with neoadjuvant or adjuvant chemotherapy. — Treatment of adult patients who have HER2-negative metastatic breast cancer with a deleterious or suspected deleterious gBRCAm, for which they have previously been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. — Maintenance treatment of adult patients who have metastatic pancreatic adenocarcinoma with a deleterious or suspected deleterious gBRCAm, which has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. — Treatment of adult patients who have metastatic castration-resistant prostate cancer (mCRPC) with a deleterious or suspected deleterious BRCA mutation (germline or somatic), which has progressed following prior therapy that included a new hormonal agent. — Treatment of adult patients who have mCRPC with a deleterious or suspected deleterious BRCA mutation (germline or somatic), in combination with abiraterone and either prednisone or prednisolone.

Dosing overview

The recommended dose of LYNPARZA (whether as monotherapy or in combination) is 300 mg twice a day, taken orally. LYNPARZA tablets should be swallowed whole (not chewed, crushed, dissolved or divided) at approximately the same time each day, and can be taken with or without food. Duration of treatment varies by indication: first-line maintenance treatment of BRCA-mutated advanced ovarian cancer is given until disease progression, unacceptable toxicity or for a maximum of 2 years unless there is remaining evidence of disease and the treating physician believes continuing treatment would provide further benefit; maintenance treatment of relapsed ovarian cancer until disease progression or unacceptable toxicity; first-line maintenance treatment of HRD-positive advanced ovarian cancer (in combination with bevacizumab) until disease progression, unacceptable toxicity or for a maximum of 2 years unless there is remaining evidence of disease; adjuvant treatment of high-risk HER2-negative gBRCAm early breast cancer until disease recurrence, unacceptable toxicity or for a maximum of 1 year, whichever occurs first; metastatic HER2-negative gBRCAm breast cancer until disease progression or unacceptable toxicity; first-line maintenance treatment of gBRCAm metastatic pancreatic adenocarcinoma until disease progression or unacceptable toxicity; and treatment of BRCAm mCRPC after prior novel hormonal agent therapy until disease progression or unacceptable toxicity.

Key safety warnings

Olaparib commonly causes haematological toxicity; while the majority were generally mild or moderate (CTCAE Grade 1 or 2), Grade 3 or higher events of anaemia (decrease in haemoglobin) occurred in 7.4% of patients in Study 19, and one patient died from a haemorrhagic stroke associated with thrombocytopenia. Patients should not start treatment with LYNPARZA until they have recovered from haematological toxicity caused by previous anti-cancer therapy (haemoglobin, platelet, and neutrophil levels should be ≤CTCAE grade 1), and full blood count should be checked at baseline, then monthly for the first year of treatment, and periodically after that. LYNPARZA may cause myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML), and the majority of events reported had a fatal outcome; the incidence of MDS/AML in patients treated in clinical trials with LYNPARZA monotherapy was 1.5%. If MDS and/or AML are confirmed while on treatment with LYNPARZA, permanently discontinue LYNPARZA. Pneumonitis has been reported in patients treated with LYNPARZA in clinical studies, including some fatal cases when used in combination with other therapies; if patients present with new or worsening respiratory symptoms such as dyspnoea, cough and fever, or an abnormal chest radiological finding is observed, LYNPARZA treatment should be interrupted and prompt investigation initiated, and if pneumonitis is confirmed, LYNPARZA treatment should be discontinued. Venous thromboembolic events (VTE), including severe or fatal pulmonary embolism (PE), have occurred in patients treated with LYNPARZA; in combined data from two randomised, placebo-controlled clinical studies (PROfound and PROpel) in patients with mCRPC who were also receiving androgen deprivation therapy (N=1180), VTE occurred in 8% of patients who received LYNPARZA, including PE in 6%. Monitor patients for clinical signs and symptoms of venous thrombosis and pulmonary embolism and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated. Cases of drug-induced liver injury (DILI) have been reported in patients treated with LYNPARZA in the post-marketing setting; if DILI is suspected, treatment should be interrupted, and if DILI is confirmed, treatment should be discontinued.

Contraindications

LYNPARZA is contraindicated in patients with hypersensitivity to the active substance (olaparib) or to any of the excipients.

PBS listing

LYNPARZA tablets 100 mg and 150 mg are listed on the PBS with 11 items each, under authority required and streamlined restrictions, at an ex-manufacturer price of A$3234.75.

Regulatory history

LYNPARZA olaparib 100 mg and 150 mg film-coated tablets were first listed on the ARTG on 23 May 2018. The PBAC recommended LYNPARZA in November 2016 for maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated high-grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who were in response to platinum-based chemotherapy, with an Authority Required (Streamlined) listing. In March 2020, the PBAC recommended amending the listing to include patients with somatic BRCA1/2 mutations in addition to germline BRCA1/2 mutations for platinum-sensitive relapsed ovarian, fallopian tube and primary peritoneal cancer. In July 2020, the PBAC recommended a change to include newly diagnosed advanced BRCA-mutated high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer in response to first-line platinum-based chemotherapy. In November 2023, the PBAC recommended LYNPARZA for treatment of HER2-negative, high-risk early breast cancer with confirmed germline BRCA1 or BRCA2 mutation who had previously been treated with neoadjuvant or adjuvant chemotherapy, noting high need for effective treatment and requiring an additional price reduction. In November 2024, the PBAC recommended a General Schedule Authority Required listing for first-line treatment of metastatic castration-resistant prostate cancer in combination with abiraterone in patients with BRCA1 or BRCA2 mutation who had not received prior novel hormonal agent therapy, noting non-inferiority to talazoparib plus enzalutamide and requiring participation in the same risk-sharing arrangement as talazoparib.