Use of Olaparib in Patients With BRCA+/HER2- High-Risk Early Breast Cancer

Charles Geyer, MD, medical oncologist/breast cancer specialist, and chief scientific officer, NSABP, discusses olaparib (Lynparza) for the treatment of patients with BRCA-positive, HER2-negative high-risk early breast cancer as evaluated in the OlympiA study (NCT02032823).

Geyer explains that within the breast cancer space, there are a number of PARP inhibitor drugs, few of which have been approved by the FDA for the use in different tumor types including breast cancer, ovarian cancer, prostate cancer and more.

Results from the phase 3 OlympiA study presented during the March 2022 ESMO Virtual Plenary, showed adjuvant olaparib to demonstrate a 32% reduction in the risk of death when compared to the placebo after a median follow-up of 3.5 years (stratified HR, 0.68; 98.5% CI, 0.47-0.97; P = .0009). The finding was statistically significant and was paired with a manageable toxicity profile.

Transcription:

0:08 | Olaparib is a first-in-class drug. In the early breast cancer setting, there are a number of these PARP inhibitor drugs. There's actually 4 or 5 that have been approved by the FDA across different tumor types. Two of them have been approved in metastatic cancer: olaparib and talazoparib [Talzenna]. They are approved specifically for patients who have germline BRCA mutations which cause cancers that develop in them to be unusually sensitive to inhibition of PARP.

0:42 | A cancer that's developed in a patient who has a germline BRCA mutation will lose all of the BRCA protein function, which is important in repairing DNA and even cancer cells have to kind of repair their DNA as they're dividing, or things can just get too chaotic, so, they become addicted to PARP. PARP inhibitors then shut that off and they are basically overwhelmed by too much instability in their DNA in the genome, so, they will die. That’s why these drugs have been active across a number of tumor types like breast cancer, ovarian cancer, prostate cancer, pancreatic cancer, and got approved in the metastatic setting.

1:33 | What is new about the OlympiA study result is that this is the first time these drugs have been taken into the early breast cancer setting to see if we can decrease recurrences, reduce deaths, and OlympiA is telling us that, yes, we can. And we use olaparib after patients who receive all their standard treatments for early breast cancer, so hat's the uniqueness of it. It's the patient population of those with germline BRCA mutation who developed breast cancer that is higher risk. The standard therapies are a bit lacking for them and we were looking for something to get in addition to it. We've now demonstrated that something is olaparib.