Clinical Trials

Date: 2017-06-04

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the American Society of Clinical Oncology (ASCO) annual meeting, in Chicago

Company: AstraZeneca (UK)

Product: Lynparza™ (olaparib)

Action mechanism:

  • poly ADP-ribose polymerase (PARP) inhibitor/enzyme inhibitor. Lynparza™ (olaparib) is an oral poly ADP-ribose polymerase (PARP) inhibitor that exploits tumour DNA repair pathway deficiencies to preferentially kill cancer cells.
  • Lynparza™ is the first PARP inhibitor to be approved for patients with germline BRCA-mutated advanced ovarian cancer, and has been launched in the U.S. and Europe. In addition to ovarian cancer, AstraZeneca is investigating the full potential of olaparib in multiple tumour types, with Phase III studies in second line gastric cancer, BRCA-mutated pancreatic cancer and adjuvant and metastatic BRCA-mutated breast cancers underway.
  • Lynparza is currently being tested in another separate adjuvant (non-metastatic) breast cancer Phase III trial called OLYMPIA.

Disease: HER2-negative metastatic breast cancer harbouring germline BRCA1 or BRCA2 mutations

Therapeutic area: Cancer - Oncology

Country: Bulgaria, China, Czech Republic, France, Hungary, Italy, Japan, Korea, Republic of, Mexico, Peru, Poland, Romania, Russian Federation, Spain, Switzerland, Taiwan, Turkey, UK, USA

Trial details: OLYMPIAD is a randomised, multi-center Phase III trial assessing the efficacy and safety of Lynparza® (300 mg twice daily) 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 study was conducted in 19 countries from across Europe, Asia, North America and South America. 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).  (NCT02000622)

Latest news:

  • • On June 4, 2017, AstraZeneca 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® (olaparib) tablets (300mg twice daily), compared to treatment with physician’s choice of a standard of care chemotherapy. 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% 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).
  • The data were presented at the 2017 ASCO Annual Meeting in Chicago. The trial was designated for the “Best of ASCO” selection, underscoring the importance of these results for patients and physicians, and the results have been published in the New England Journal of Medicine.
  • 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.
  • 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).i In addition, the objective response rate (ORR) was more than doubled, with 59.9% of patients in the Lynparza arm showing response to treatment, compared to 28.8% of patients treated with chemotherapy.i
  • A review of the Lynparza®  safety data from the OlympiAD trial did not identify any new safety signals and the overall safety profile was consistent with previous trials of Lynparza®. 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).
  • • On February 17, 2017, AstraZeneca announced positive results from its Phase III OLYMPIAD trial comparing Lynparza® (olaparib) tablets (300mg twice daily) to physician’s choice of a standard of care chemotherapy in the treatment of patients with HER2-negative metastatic breast cancer harbouring germline BRCA1 or BRCA2 mutations. Patients treated with Lynparza® showed a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) compared with those who received chemotherapy (capecitabine, vinorelbine or eribulin). Initial findings from the OLYMPIAD study indicate that the safety profile of Lynparza® was consistent with previous studies. A full evaluation of the OLYMPIAD data is ongoing and the results will be submitted for presentation at a forthcoming medical meeting. AstraZeneca will be working with regulatory authorities to make Lynparza® available to patients with this type of breast cancer.

Is general: Yes