LYNPARZA (OLAPARIB) ACCEPTED FOR USE IN SCOTLAND TO TREAT GERMLINE BRCA-MUTATED HER2-NEGATIVE LOCALLY ADVANCED OR METASTATIC BREAST CANCER AFTER CHEMOTHERAPY

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

– ENDS –

CONTACTS

UK Media Enquiries

Emma White, AstraZeneca: 07385 516437 / emma.white1@astrazeneca.com

Lucie Foster, Edelman: 07891 869948 / lucie.foster@edelman.com

NOTES TO EDITORS

About Lynparza (olaparib)

Olaparib was the first cancer drug in the world to be licensed to target inherited genetic faults.¹³ Olaparib is a potent inhibitor of human poly (ADP-ribose) polymerase (PARP) enzymes that are targeted to block DNA repair in cancer cells harbouring a deficiency in homologous recombination repair (HRR), such as those with mutations in BRCA1 and/or BRCA2.¹²

Inhibition of PARP proteins with olaparib leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse, and the generation of DNA double-strand breaks (DSBs) and cancer cell death.[20]

Olaparib is also indicated in the United Kingdom for adjuvant treatment of HER2‑negative high-risk early breast cancer that has been treated with neoadjuvant or adjuvant chemotherapy in adults with germline BRCA1 or 2 mutations.[21]

For complete information on olaparib, the summary of product characteristics, including a full list of side effects and adverse reactions, is available here: https://www.medicines.org.uk/emc/product/9204/smpc#gref.

About OlympiAD

OlympiAD was a global, randomised, open-label, multi-centre Phase III trial of 302 patients, to assess the efficacy and safety of olaparib tablets (300mg twice daily) compared to chemotherapy (capecitabine, eribulin or vinorelbine).¹¹ 205 patients were randomised to receive olaparib and 97 patients were randomised to receive chemotherapy.¹¹

Patients in the OlympiAD trial had germline BRCA1 and/or BRCA2-mutated, HER2-negative (HR-positive or triple negative) breast cancer and received olaparib for treatment in the metastatic setting.¹¹ Before enrolment, all patients were treated with anthracycline (unless it was contraindicated) and taxane chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.¹¹

Patients with metastatic breast cancer had received no more than two previous chemotherapy treatments for metastatic disease.¹¹ Patients with HR-positive breast cancer had received at least one endocrine (hormonal) therapy (in the adjuvant or metastatic setting) and had disease progression during therapy, unless they had disease for which endocrine therapy was considered inappropriate.¹¹ Previous treatment with platinum chemotherapy in the neoadjuvant, adjuvant or metastatic setting was allowed.¹¹

In the trial, olaparib provided patients with a significant median progression-free survival improvement of 2.8 months (HR 0.58; 95% CI 0.43-0.80; p<0.001 median progression-free survival 7.0 months for olaparib vs. 4.2 months for chemotherapy).¹¹ Patients taking olaparib experienced an objective response rate (ORR) of 59.9% vs 28.8% in the chemotherapy arm.¹¹

About advanced breast cancer

Advanced/metastatic breast cancer refers to Stage IV breast cancer.[22] Metastatic disease is the most-advanced stage of breast cancer and occurs when cancer cells have spread beyond the initial tumour site to other organs of the body outside the breast.²² Since there is no cure for the disease, the goal of current treatment is to delay disease progression or death.[23]^,[24]

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its medicines are used by millions of patients worldwide.

With a proud 100-year heritage in advancing UK science, today AstraZeneca is the UK’s leading biopharmaceutical company. The company is based in five separate locations across the UK, with its global headquarters in Cambridge. In the UK, around 8,700 employees work in research and development, manufacturing, supply, sales, and marketing. We supply around 36 different medicines to the NHS.

For more information, please visit www.astrazeneca.co.uk and follow us on Twitter @AstraZenecaUK.

References

[1] Scottish Medicine Consortium. Olaparib film-coated tablets (Lynparza^®): Detailed advice document SMC2737 – published 10 February 2025.

[2] West of Scotland Cancer Network. Breast Cancer. Available at: https://www.woscan.scot.nhs.uk/managed-clinical-networks/nhs-woscan-breast-cancer-homepage/#:~:text=Breast%20cancer%20is%20the%20most%20common%20cancer%20in,Scotland%2C%20with%20approximately%204500%20new%20cases%20diagnosed%20annually. Last accessed: February 2025.

[3] Breast Cancer Now. We respond 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: February 2025.

[4] The University of Edinburgh. Two founder variants account for 90% of pathogenic BRCA alleles in Orkney and Shetland. Available at: https://viking.ed.ac.uk/research/two-founder-variants-90-percent-brca-alleles-orkney-shetland. Last accessed: February 2025.

[5] Breast Cancer Now. Breast Cancer Facts and Statistics. Available at: https://breastcancernow.org/about-us/why-we-do-it/breast-cancer-facts-and-statistics/. Last accessed: February 2025.

[6] 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: February 2025.

[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: February 2025.

[10] Mehrgou A, et al. The importance of BRCA1 and BRCA2 genes mutations in breast cancer development. Med J Islam Repub Islam. 2016;30:369.

[11] 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.

[12] DrugBank: Available at: https://go.drugbank.com/drugs/DB09074. Last accessed February 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: February 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: February 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.

[20] Electronic Medicines Compendium (EMC). Lynparza 100mg Film-Coated Tablets - Summary of Product Characteristics (SmPC). Available at: https://www.medicines.org.uk/emc/product/9204/smpc. Last accessed: February 2025.

[21] National Institute for Health and Care Excellence. Olaparib for adjuvant treatment of BRCA mutation-positive HER2-negative high-risk early breast cancer after chemotherapy. Available at: https://www.nice.org.uk/guidance/ta886/resources/olaparib-for-adjuvant-treatment-of-brca-mutationpositive-her2negative-highrisk-early-breast-cancer-after-chemotherapy-pdf-82613736977605#:~:text=Olaparib%20(alone%20or%20with%20endocrine,germline%20BRCA1%20or%202%20mutations. Last accessed: February 2025.

[22] Cleveland Clinic. Metastatic Breast Cancer. Available at: https://my.clevelandclinic.org/health/diseases/21497-metastatic-breast-cancer. Last accessed: January 2025.

[23] Breast Cancer Org. Metastatic Breast Cancer. Available at: https://www.breastcancer.org/types/metastatic. Last accessed: January 2025.

[24] Rugo HS, et al. Cancer treatment options for metastatic breast cancer: what now? Clin Adv Hematol Oncol. 2011;9(11 Supply 25):1-16.