NICE RECOMMENDS LYNPARZA (OLAPARIB) TO TREAT GERMLINE BRCA-MUTATED HER2-NEGATIVE LOCALLY ADVANCED OR METASTATIC BREAST CANCER AFTER CHEMOTHERAPY IN ENGLAND AND WALES
- NICE's decision was informed by positive results from the pivotal OlympiAD Phase III trial.[1]
- Breast cancer is the most common cancer in the UK, making up 15% of all new cancer cases.[2] In the UK, a woman is diagnosed with breast cancer every 10 minutes.[3]
- 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.[4]
London, UK, Thursday 9 January 2025 – Today, AstraZeneca announced that Lynparza (olaparib) has received a positive recommendation from the National Institute for Health and Care Excellence (NICE) for NHS use in England and Wales to treat adults with HER2-negative, locally advanced or metastatic breast cancer with germline BRCA1 or BRCA2 mutations after chemotherapy.[5]
Germline BRCA1 and BRCA2 mutations are responsible for about 52% and 32% of hereditary breast cancer respectively and 5% to 10% of all breast cancers.[6] Genetic testing is essential to 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 - regardless of gender.[9] This means that both daughters and sons can inherit these mutations, which not only significantly increases the risk of breast cancer but are also associated with higher risks of ovarian, pancreatic, and prostate cancers.9,[10] Testing for BRCA mutations for eligible patients is available and reimbursed by the NHS via the National Genomic Test Directory.[11]
Professor Andrew Tutt, Director of the Toby Robins Breast Cancer Now Research Centre at The Institute of Cancer Research, London and King’s College London, one of the team who developed olaparib for patients for BRCA-mutations, said: “Locally advanced or metastatic HER2-negative breast cancer remains a devastating diagnosis. For those with this form of breast cancer and with inherited BRCA-mutations, the OlympiAD Phase III trial demonstrated how olaparib – a PARP inhibitor that targets the mutated BRCA genes in cancer cells – can significantly delay cancer progression or death compared to standard chemotherapies. These results underpinned this positive NICE recommendation, which now provides another important oral targeted therapy option for our patients with this challenging diagnosis. This emphasises the importance of accessing genetic testing, so that these targeted drugs can reach the patients who will benefit from them.”
NICE based this determination on positive results from the pivotal OlympiAD Phase III trial.1 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.1 The safety profile of olaparib from the trial was consistent with the known safety profile of olaparib.1
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
Tom Keith-Roach, President, AstraZeneca UK, said: “We are delighted that NICE has recommended olaparib to treat patients with HER2-negative, locally advanced or metastatic breast cancer with germline BRCA-mutations. This decision is AstraZeneca's 26th cancer medicine recommendation from NICE and the SMC since 2021 further demonstrating our unwavering commitment to revolutionising cancer care in the UK, taking us one step closer to one day eliminating cancer as a cause of death.”
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%). The percentage of patients who discontinued treatment in the olaparib arm was 5% vs. 8% in the chemotherapy arm.1
[1] Robinson M. et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. New England Journal of Medicine, 2017;377:523-533
[2] Breast Cancer UK. About Breast Cancer Facts and Figures. Available at: https://www.breastcanceruk.org.uk/about-breast-cancer/facts-figures-and-qas/facts-and-figures/. Last accessed: January 2025.
[3] Breast Cancer Now. Breast Cancer Facts. Available at: https://breastcancernow.org/about-us/why-we-do-it/breast-cancer-facts-and-statistics/#:~:text=develop%20breast%20cancer%3F-,Breast%20cancer%20is%20the%20most%20common%20cancer%20in%20the%20UK,are%20diagnosed%20with%20breast%20cancer. Last accessed: January 2025.
[4] Breast Cancer Now. We responses to research identifying new rare genes associated with breast cancer. Available at: https://breastcancernow.org/about-us/media/statements/we-respond-to-research-identifying-new-rare-genes-associated-with-breast-cancer/. Last accessed: January 2025.
[5] National Institute for Health and Care Excellence. Final Draft Guidance. Olaparib for treating BRCA mutation-positive HER2-negative advanced breast cancer after chemotherapy. Issue date: 9 January 2025.
[6] Mehrgou A, et al. The importance of BRCA1 and BRCA2 genes mutations in breast cancer development. Med J Islam Repub Islam. 2016;30:369.
[7] Ahn S, et al. Genetic testing in patients with newly diagnosed breast cancer: Room for improvement. J Clin Oncol. 2017;35(20):2221-2223.
[8] Tung N, et al. Germline genetic testing for women with breast cancer: Shifting the paradigm from whom to test to whom NOT to test. J Clin Oncol. 2021;39(31):3415-3418.
[9] Be BRCA Aware. Available at: https://www.bebrcaware.com/resources/mutations#:~:text=Certain%20BRCA%20mutations%20are%20hereditary,family%20members%20regardless%20of%20gender.&text=or%20caregiver.,chance%20of%20inheriting%20the%20mutation. Last accessed: January 2025.
[10] National Cancer Institute. BRCA Gene Changes: Cancer Risk and Genetic Testing. Available at: https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet. Last accessed: January 2025.
[11] NHS England. National genomic test directory rare and inherited disease. Available at: rare-and-inherited-disease-national-genomics-test-directory-official-V7.1.xlsx. Last Accessed: January 2025.
[12] DrugBank: Available at: https://go.drugbank.com/drugs/DB09074. Last accessed January 2025.
[13] NIHR. Olaparib: the journey of a world-first drug. Available at: https://www.cancerbrc.org/advance/olaparib-journey-world-first-drug. Last accessed: January 2025.
[14] NHS UK. Clinical Commissioning Policy: Genetic Testing for BRCA1 and BRCA2 Mutations. Available at: https://www.england.nhs.uk/wp-content/uploads/2018/07/Genetic-testing-for-BRCA1-and-BRCA2-mutations.pdf. Last accessed: January 2025.
[15] Zámborszky, J. Loss of BRCA1 or BRCA2 markedly increases the rate of base substitution mutagenesis and has distinct effects on genomic deletions. Oncogene 36, 746–755 (2017).
[16] Roy R, et al. BRCA1 and BRCA2: Different Roles in a Common Pathway of Genome Protection. Nat Rev Cancer. 12(1):68-78.
[17] Wu J, et al. The Role of BRCA1 in DNA Damage Response. Protein Cell. 2010;1(2):117-123.
[18] Gorodetska I, et al. BRCA Genes: The Role in Genome Stability, Cancer Stemness and Therapy Resistance. J Cancer. 2019;10(9):2109-2127.
[19] Li H, et al. PARP Inhibitor Resistance: The Underlying Mechanisms and Clinical Implications. Mol Cancer. 2020;19:107.
