Positive results for AstraZeneca’s PARP inhibitor Lynparza in advanced breast cancer

By Dr. Ananya Mandal, MDJun 5 2017

A new study has shown that AstraZeneca's Lynparza (olaparib) can significantly slow the progress of breast cancer that is caused partially due to mutations of the culprit gene called BRCA. BRCA gene mutations are responsible for around 3% of all breast cancers. These cases of the disease that have a basis in the gene are notoriously difficult to treat and women who are tested positive for this gene may even opt for removal of their breasts before even the cancer strikes. Noted actress Angelina Jolie went for a similar prophylactic mastectomy.

This new study termed as the OlympiAD trial, included 302 women with breast cancer that has spread to other organs. This was a Phase III clinical trial. They were positive for BRCA gene mutation. When analyzed, their breast cancer cells had to have one of the two hormone sensing molecules (Estrogen and Progesterone) or have none of these two hormone receptors along with HER2 molecule. These cancers are termed “triple negative breast cancers”.

Results showed that Lynparza reduced the risk of the cancer growing by as much as 42% compared to other standard chemotherapy and also showed much less side effects that conventional chemotherapy. In 60% patients receiving Lynparza, the tumor showed evident shrinkage. Similar shrinkage was noted in 29% women on conventional chemotherapy. Disease progression of these cancers is usually measured in months. It was 4.2 months with conventional chemotherapy that women were detected with progression of the disease. On the other hand women who were on Lynparza went 7 months before their cancer progressed any further. Serious side effects were seen in 37% women on Lynparza compared to 50% in women on conventional chemotherapy.

Lynparza (olaparib) is one of the much anticipated and researched medicines as it inhibits the enzyme poly ADP ribose polymerase (PARP). Lynparza (olaparib) is termed a PARP inhibitor. BRCA gene works by stopping the repair of the damage caused by the cancer to the DNA. PARP further stops the damage repair by the cells. Lynparza can work only on cancers where the BRCA gene mutation is the culprit.

Lynparza is already in the market for ovarian cancer that is caused by BRCA. Two other similar drugs for BRCA mutation induced ovarian cancer include Zejula and Rubraca manufactured and made by Tesaro and Clovis Oncology respectively. Lynparza sales are projected to grow to $684 million by 2020 because of its success in ovarian as well as breast cancer. A study of this drug in pancreatic cancer is slated to reach the readers by next years and the drug is also being studied in prostate cancer. Another trial using Olaparib called PARTNER is underway atpresent to check on the sustained benefits of this drug in breast cancer. This trial is supported by Cancer Research UK.

Meanwhile the AstraZeneca funded OlympiAD trial results were presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago in the United States. The results are published in the New England Journal of Medicine. Dr Mark E. Robson, Clinic Director of the Clinical Genetics Service and medical oncologist at Memorial Sloan Kettering Cancer Center in New York, who led the study said that this was the first study that showed improvement of BRCA mutation associated breast cancer with a PARP inhibitor. This could pave the way for new therapies and approaches to breast cancer treatment.