Lynparza® (olaparib) significantly reduces the risk of disease worsening or death in patients with brca-mutated metastatic breast cancer

OlympiAD was the first positive Phase III trial to evaluate the efficacy and safety of a PARP inhibitor beyond ovarian cancer

Lynparza tablets reduced risk of disease worsening or death by 42 per cent

The overall safety profile was consistent with previous trials of Lynparza

MISSISSAUGA, ON, June 4, 2017 /CNW/ – AstraZeneca today presented positive results from its Phase III OlympiAD trial that showed a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) for patients treated with Lynparza tablets (300mg twice daily), compared to treatment with physician’s choice of a standard of care chemotherapy.1 In addition to meeting its primary endpoint of PFS assessed by blinded independent central review (BICR), the trial showed that patients treated with Lynparza had a 42 per cent reduction in risk of their disease worsening or death (HR 0.58; 95% CI 0.43,0.80; p=0.0009; median 7.0 vs 4.2 months) compared to those who received chemotherapy (capecitabine, vinorelbine, eribulin).1

The data were presented at the 2017 ASCO Annual Meeting in Chicago, during today’s Plenary Session from 15:10 – 15:25 CDT (Abstract LBA4).1 Additionally, the trial was designated the “Best of ASCO” selection, underscoring the importance of these results for patients and physicians.

“The demonstrated benefit of Lynparza compared with chemotherapy in the OlympiAD study comes as welcome news for women with BRCA-mutated metastatic breast cancer,” said Dr. Karen Gelmon, Medical Oncologist, British Columbia Cancer Agency and Professor of Medicine, University of British Columbia. “There is a high unmet need when it comes to treating BRCA- mutated metastatic breast cancer. These results mean that this well tolerated oral treatment may provide prolonged progression-free survival for some of these women, offering a non- chemotherapy treatment alternative.”

Patients in the trial had HER2-negative germline BRCA1 or BRCA2-mutated breast cancer and were receiving Lynparza as their first, second or third-line medicine for metastatic disease. Before enrolment, patients had prior treatment with an anthracycline (unless contraindicated) and a taxane; hormone receptor-positive patients received at least one endocrine medicine or were not eligible for endocrine medicines.1

Secondary endpoints showed an improvement in time until second progression or death (PFS2) in the Lynparza arm of the trial, compared to those treated with chemotherapy (HR 0.57; 95% CI:

0.40-0.83).1 In addition, the objective response rate (ORR) was more than doubled, with 59.9 per cent of patients in the Lynparza arm showing response to treatment, compared to 28.8 per cent of patients treated with chemotherapy.1

“The OlympiAD study results are very promising as this is the first time a targeted therapy has shown benefit over the current standard of care for patients with HER2-negative gBRCA mutated metastatic breast cancer,” said Dr. Neil Maresky, Vice President, Scientific Affairs with AstraZeneca Canada. “This also marks an important milestone for Lynparza as this is the first positive Phase III study in which a PARP inhibitor has shown clinical value for patients outside of ovarian cancer.”

A review of the Lynparza safety data from the OlympiAD trial was consistent with previous Lynparza trials and did not identify any new safety signals. There was a lower incidence of grade ≥3 adverse events in the Lynparza arm compared to the chemotherapy arm (36.6% vs 50.5% respectively). A smaller proportion of patients discontinued treatment in the Lynparza arm compared to the chemotherapy arm (4.9% vs 7.7% respectively).1

About OlympiAD1

OlympiAD is a randomized, open label, multi-centre Phase III trial assessing the efficacy and safety of Lynparza (300 mg tablets twice daily) compared to ‘physician’s choice’ chemotherapy (capecitabine, vinorelbine, eribulin) in 302 patients with HER2-negative metastatic breast cancer with germline BRCA1 or BRCA2 mutations, which are predicted or suspected to be deleterious. The international trial was conducted in 19 countries from across Europe, Asia, North America (including Canada) and South America.

Within the eligible patient population, there was a 1:1 ratio between triple-negative breast cancer (TNBC) and hormone receptor positive (ER+ and/or PR+) patients.

The primary endpoint of the trial was progression-free survival (PFS) as measured by a Blinded Independent Central Review (BICR). Secondary endpoints include overall survival (OS), time to second progression or death (PFS2), objective response rate (ORR), and effect on health-related quality of life (HRQoL).

About Lynparza® (olaparib)

Lynparza is a first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that may exploit tumour DNA damage response (DDR) pathway deficiencies to preferentially kill cancer cells. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of approved and potential new medicines targeting DDR mechanisms in cancer cells. It is the first PARP inhibitor to be approved as a maintenance therapy for patients with platinum-sensitive relapsed BRCA-mutated (germline or somatic) ovarian cancer. Health Canada’s Notice of Compliance with Conditions for Lynparza on April 29, 2016 follows the announcement of the approval of Lynparza by the FDA on December 19, 2014 and in the European Union on December 18, 2014. AstraZeneca is conducting multiple Lynparza Phase III studies across a variety of indications and tumour types.

About Metastatic Breast Cancer in Canada2

Thirty per cent of women diagnosed with early stage breast cancer will go on to develop metastatic breast Cancer. Approximately 10 per cent of all newly diagnosed breast cancers are metastatic at diagnosis. Despite the new development of treatment options, there is currently no cure for patients with metastatic breast cancer, thus, the primary aim of treatment is to slow progression of the disease for as long as possible and improve or maintain a patient’s quality of life.

About Germline BRCA mutations

BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role in maintaining the genetic stability of cells. When either of these genes is mutated or changed, its protein is either faulty or not made at all and DNA damage may not be repaired properly. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.3

BRCA1 and BRCA2 mutations account for about 10 per cent of all breast cancers and up to 25 per cent of hereditary cases. Approximately 15 per cent of all ovarian cancer patients harbour a BRCA mutation. Breast and ovarian cancers develop earlier in women with BRCA mutations compared to those without the mutation.4, 5

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialization of primary and specialty care medicines that transform lives. Our primary focus is on three important areas of healthcare: Cardiovascular and Metabolic disease; Oncology; and Respiratory, Inflammation and Autoimmunity. AstraZeneca operates in more than 100 countries and its innovative medicines are used by millions of patients worldwide. In Canada, we employ more than 720 employees across the country and our AstraZeneca Canada headquarters are located in Mississauga, Ontario. For more information, please visit the company’s website at www.astrazeneca.ca.

CONTACT: Michelle Marchione, Senior Manager, Corporate Communications AstraZeneca Canada Tel: 905-803-5749 Email: michelle.marchione@astrazeneca.com


 

References:

1 Robson, Mark MD, et al. OlympiAD: Phase III trial of olaparib monotherapy versus chemotherapy for patients (pts) with HER2-negative metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm). In: 2017 ASCO Annual Meeting; June 2 – 6, 2017; Chicago, Illinois; Abstract LBA4.

2 Canadian Cancer Society. Living with Metastatic Breast Cancer. Available at: http://www.cbcf.org/central/AboutBreastCancerMain/MetastaticBreastCancer/Pages/default.aspx. Accessed May 29, 2017.

3 National Cancer Institute. BRCA1 and BRCA2: Cancer Risk and Genetic Testing. Available at: https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet. Accessed June 1, 2017.      

4 Easton DF. How many more breast cancer predisposition genes are there? Breast Cancer Research 1999; 1(1):14– 17.

5 Campeau PM, Foulkes WD, Tischkowitz MD. Hereditary breast cancer: New genetic developments, new therapeutic avenues. Human Genetics 2008; 124(1):31–42.

Lynparza® is a registered trademark of AstraZeneca AB, used under license by AstraZeneca Canada Inc.