AstraZeneca today presented positive Phase III results showing its poly(ADP-ribose) polymerase (PARP) inhibitor Lynparza™ (olaparib) delivered clinically meaningful improvement in progression-free survival (PFS) compared to chemotherapy in patients with BRCA-mutated metastatic breast cancer.

The results, presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, marked the first time a PARP inhibitor generated significant positive efficacy and safety results beyond ovarian cancer, for which Lynparza has been approved in the U.S. since 2014.

The Phase III OlympiAD trial was designed to compare the efficacy and safety of Lynparza 300 mg tablets twice daily to “physician’s choice” chemotherapy (capecitabine, vinorelbine, eribulin) in 302 patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer with germline BRCA1 or BRCA2 mutations predicted or suspected to be deleterious.

Of patients treated with Lynparza, approximately 60% saw significant tumor shrinkage compared with 29% treated with chemotherapy. PFS was measured by a blinded independent central review (BICR)—and the results elaborated on the topline success trumpeted by AstraZeneca back in February.

“The OlympiAD results shared today mark the first time a targeted therapy shows benefit over the current standard of care for patients with HER2-negative germline BRCA-mutated metastatic breast cancer,” Sean Bohen, M.D., Ph.D., evp, global medicines development and CMO, AstraZeneca, said in a statement.

Lynparza also showed positive results in several secondary outcomes:

  • Overall survival (OS): The trial showed that patients treated with Lynparza had a 42% reduction in risk of their disease worsening or death compared to those who received chemotherapy (median 7.0 vs 4.2 months).
  • Time to second progression or death (PFS2): Lynparza patients showed a 43% improvement compared to those treated with chemotherapy.
  • Objective response rate (ORR): AstraZeneca said the ORR was more than doubled among Lynparza patients, with 59.9% of them showing response to treatment compared to 28.8% of patients treated with chemotherapy.

Patients received Lynparza as a first-, second-, or third-line medicine for metastatic disease. Before enrollment, 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.

Safety data from the OlympiAD trial showed an overall safety profile consistent with previous trials of Lynparza. Data included a lower incidence of grade ≥3 adverse events in the Lynparza arm compared to the chemotherapy arm (36.6% vs. 50.5%, respectively) and a smaller proportion of patients discontinuing treatment with Lynparza compared to chemotherapy (4.9% vs. 7.7%, respectively).

Results from OlympiAD were published in The New England Journal of Medicine (“Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation”). The global trial was conducted in 19 countries across Europe, Asia, North America, and South America.

“The OlympiAD data presented today demonstrate the benefit of olaparib in delaying the progression of advanced BRCA-mutated breast cancer.  With few alternatives available, a targeted nonchemotherapy oral treatment in this setting could be a beneficial new option for patients,” added Mark E. Robson, M.D., principal investigator of OlympiAD and clinic director of the Clinical Genetics Service at Memorial Sloan Kettering Cancer Center.








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