LYNPARZA (olaparib) APPROVED IN GREAT BRITAIN AS ADJUVANT TREATMENT FOR PATIENTS WITH GERMLINE BRCA-MUTATED HER2-NEGATIVE HIGH-RISK EARLY BREAST CANCER

STRICTLY EMBARGOED UNTIL Tuesday 6 September 2022 00:01 BST

LYNPARZA (olaparib) APPROVED IN GREAT BRITAIN AS ADJUVANT TREATMENT FOR PATIENTS WITH GERMLINE BRCA-MUTATED HER2-NEGATIVE HIGH-RISK EARLY BREAST CANCER

• First and only approved medicine in Great Britain which targets germline BRCA mutations in patients with early breast cancer (stage I-IIIA) previously treated with neoadjuvant or adjuvant chemotherapy.
• The decision is based on positive data from the OlympiA Phase III trial which showed a statistically significant and clinically meaningful improvement in three-year invasive disease-free survival (iDFS), reducing the risk of invasive breast cancer recurrences, second primary invasive cancers or death, by 42% versus placebo. 0F^[1]
• Approximately 150 people are diagnosed with breast cancer each day in the UK1F^[2] and around 90% of patients are diagnosed at an early-stage of disease.2F^[3]

London, UK, Tuesday 6 September 2022 – AstraZeneca today announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation for Lynparza (olaparib) in Great Britain for use as monotherapy or in combination with endocrine therapy for the adjuvant treatment of adult patients with germline BRCA1 or BRCA2 mutations, who have HER2-negative high risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy.3F^[4]

Breast cancer is the most diagnosed cancer worldwide with an estimated 2.3 million patients diagnosed per year.4F^[5] Almost 56,000 people are diagnosed with breast cancer per year in the UK, around 150 per day, accounting for 15% of all cancer cases.2 Roughly 90% of all breast cancer patients in are diagnosed at an early stage of disease (stage I-IIIA)3 and BRCA mutations are found in approximately 5% of patients.5F^[6] Despite breast cancer survival improving,2 one in three women may still experience a recurrence.6F^[7],7F^[8] When the cancer recurs, it is incurable.8F^[9]

Professor Andrew Tutt, Global Chair of the OlympiA Phase III trial and Professor of Oncology at The Institute of Cancer Research, London and King’s College London, said: “Today’s approval marks a new era of care in the UK for patients with an inherited form of breast cancer. For patients with high-risk early-stage breast cancer, including those with germline BRCA mutations, recurrence rates remain unacceptably high, with more than one in four of these patients seeing their cancer return following surgery and systemic treatment. Olaparib is a targeted treatment option that exploits the specific biology of this inherited type of breast cancer and was shown to improve survival and help prevent cancer recurrence. I am hopeful it will become a new standard of care.”

The decision from the MHRA was based on results from the OlympiA Phase III trial. In the primary endpoint of the trial, there was a statistically significant and clinically meaningful improvement in three-year invasive disease-free survival (iDFS), reducing the risk of invasive breast cancer recurrences, second primary invasive cancers or death, by 42% versus placebo (based on a hazard ratio [HR] of 0.58; 99.5% confidence interval [CI] 0.41-0.82; p<0.001).1

In one secondary endpoint of the OlympiA trial, data also showed that olaparib demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), reducing the risk of death by 32% versus placebo (based on a HR of 0.68; 95% CI 0.50-0.91; p=0.0091).1 The safety and tolerability profile of olaparib in this trial was in line with that observed in prior clinical trials.1

The decision announced today means that olaparib is now also licenced in patients with germline BRCA1 or BRCA2 mutations, who have HER2-negative high risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy.⁴          

Tom Keith-Roach, President, AstraZeneca UK, said: “We’re delighted that olaparib is the first medicine in the germline BRCA-mutated HER2-negative high risk early-stage breast cancer setting to be approved by the MHRA, and we are now working with the NHS to secure access as quickly as possible for patients in the UK. Today’s decision builds further momentum in our mission to advance the UK as a life science powerhouse and continue our collaboration and innovation to support the wider healthcare system.”

Arun Krishna, Head of Oncology, AstraZeneca UK, said: “Earlier diagnosis and the development of cutting-edge treatments are vital for improving outcomes for people with breast cancer. This approval marks a significant step forward for patients with inherited BRCA-mutated, HER2-negative high-risk early-stage breast cancer. These data highlight the importance of germline BRCA testing as soon as possible following diagnosis to provide patients with the best chance of survival.”

Across the OlympiA Phase III trial, the most common adverse reactions in the olaparib treatment arm (n=911) included: nausea (56.9% all grades; 0.8% > grade 3), fatigue (40.1% all grades; 1.8% > grade 3), anaemia (23.5% all grades; 8.7% > grade 3), vomiting (22.6% all grades; 0.7% > grade 3), headache (19.8% all grades; 0.2% > grade 3), diarrhoea (17.6% all grades; 0.3% > grade 3), decreased neutrophil count (16.0% all grades; 4.8% > grade 3), decreased white cell count (15.7% all grades; 3.0% > grade 3), decreased appetite (13.1% all grades; 0.2% > grade 3), dysgeusia (11.7% all grades; 0% > grade 3), dizziness (11.4% all grades; 0.1% > grade 3), arthralgia (9.2% all grades; 0.2% > grade 3).1

[1] Tutt A, et al. Pre-specified event driven analysis of overall survival (OS) in the OlympiA phase III trial of adjuvant olaparib (OL) in germline BRCA1/2 mutation (gBRCAm) associated breast cancer. Oral presentation. Presented at the 2022 ESMO Virtual Plenary Session, 16–18 March 2022.

[2] Cancer Research UK. Breast cancer statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/breast-cancer#heading-Zero Last accessed September 2022.

[3] Cardoso F, et al. Locally recurrent or metastatic breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2012;23:vii11-9.

[4] 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 September 2022.

[5] Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians. 2020;71:209-249.

[6] Peto J, Collins N, Barfoot R, et al. Prevalence of BRCA1 and BRCA2 Gene Mutations in Patients With Early-Onset Breast Cancer. JNCI. 1999;91;11:943-949.

[7] Colleoni M, et al. Annual Hazard Rates of Recurrence for Breast Cancer During 24 Years of Follow-Up: Results From the International Breast Cancer Study Group Trials I to V. Journal of Clinical Oncology. 2016;9:927-35.

[8] Riggio AI, et al. The lingering mysteries of metastatic recurrence in breast cancer. British Journal of Cancer. 2021;124:13–26.

[9] Breast Cancer Now. Breast cancer recurrence. Available at: https://breastcancernow.org/information-support/facing-breast-cancer/diagnosed-breast-cancer/your-primary-cancer-has-come-back-recurrence. Last accessed September 2022.