LYNPARZA (OLAPARIB) ACCEPTED FOR USE IN SCOTLAND TO TREAT GERMLINE BRCA-MUTATED HER2-NEGATIVE LOCALLY ADVANCED OR METASTATIC BREAST CANCER AFTER CHEMOTHERAPY
- Acceptance by the Scottish Medicines Consortium (SMC) was based on pivotal data from the OlympiAD Phase III clinical trial.[1]
- Breast cancer is the most common cancer amongst women in Scotland, with approximately 4,500 new cases diagnosed annually.[2]
- Around 5-10% of women with breast cancer carry a germline (inherited) altered gene - of which the BRCA 1 and 2 genes are the most common.[3]
- In the Scottish Northern Isles of Orkney and Shetland, just two gene variants account for >90% of inherited cancer risk from BRCA variants.[4]
London, UK, Monday 10 February 2025 – Today, AstraZeneca announced that Lynparza (olaparib) has been accepted for use within NHS Scotland by the Scottish Medicines Consortium (SMC) to treat adults with HER2-negative, locally advanced or metastatic breast cancer with germline BRCA1 or BRCA2 mutations after chemotherapy.1
In Scotland, nearly 5,000 people are diagnosed with breast cancer each year.[5] Mutations in the BRCA genes significantly increase the risk of developing breast cancer and are found in approximately 5-10% of all breast cancer patients.3,[6] Genetic testing is an essential part of the diagnosis and optimal care of patients with breast cancer.[7],[8] Individuals with these mutations have a 50% chance of passing the gene variant to their children.[9] This makes BRCA mutations the leading cause of hereditary breast cancer cases.[10] In the Scottish Northern Isles of Orkney and Shetland, it has been shown that just two gene variants account for nearly all (>90%) of the inherited cancer risk from BRCA variants.4 This is a stark contrast to the situation in the general UK population, where over 350 variants would need to be tested to account for the same proportion of cancer risk from BRCA variants.4 The evidence suggests an increased need for BRCA screening for people with familial risk factors in Scotland, versus the general population of the UK.
Professor David Cameron, Professor of Oncology at Edinburgh University and Director of Cancer Services at NHS Lothian, said: “Metastatic breast cancer is a challenging diagnosis for patients, who have to expect shortened survival, often experiencing low health-related quality of life, and a significant burden from its treatment. For those women whose breast cancer has arisen on a background of an inherited (germline) alteration in the BRCA1 or BRCA2 genes, olaparib offers patients a treatment option, with data from the OlympiAD Phase III trial, demonstrating a significant delay in cancer progression or death compared to standard chemotherapies, and to do so as a tablet therapy. This recommendation by the SMC represents a significant milestone for patients in Scotland, addressing an unmet need for targeted therapies for those living with BRCA-mutated HER2-negative breast cancer.”
Today’s decision from the SMC was based on positive results from the pivotal OlympiAD Phase III trial.[11] In addition to meeting its primary endpoint of median progression-free survival (PFS) assessed by blinded independent central review (BICR), the trial showed that patients treated with olaparib had a 42% reduction in risk of their disease worsening or death (HR 0.58; 95% CI 0.43-0.80; p<0.001 median progression-free survival 7.0 vs 4.2 months) compared to those who received chemotherapy.11 The safety profile of olaparib from the trial was consistent with the known safety profile of olaparib.11
Tom Keith-Roach, President, AstraZeneca UK, said: “This is a significant step forward for Scottish breast cancer patients with germline BRCA-mutations. We look forward to NHS Scotland expanding BRCA gene testing eligibility to this patient group.”
Olaparib, a product of British science and innovation, is a precision medicine and PARP (poly-ADP ribose polymerase) inhibitor, a targeted cancer therapy that helps damaged cells repair themselves.[12],[13] As a cancer treatment, olaparib targets PARP to disrupt the DNA-repair process and potentially kill tumour cells.12
BRCA1 and BRCA2 are human genes that produce proteins that repair damaged DNA and play an important role in maintaining cells' genetic stability.[14] When these genes become mutated, or altered, such that their protein product either is not made or does not function correctly, DNA damage may not be repaired, and these cells become unstable.[15] As a result, the cells are more likely to develop additional genetic alterations that can lead to cancer and confer sensitivity to PARP inhibitors including olaparib.[16],[17],[18],[19]
The most common adverse reactions (≥20%) in the OlympiAD trial of patients who received olaparib were nausea (58%), anaemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhoea (21%), and headache (20%).11 The percentage of patients who discontinued treatment in the olaparib arm was 5% vs. 8% in the chemotherapy arm.11
