Nadine M. Tung, MD
PARP inhibitors, having shown success in ovarian cancer, have finally made it to the treatment paradigm for patients with BRCA
-positive breast cancers, explains Nadine M. Tung, MD.
-positive breast cancer and the importance of genetic testing.
OncLive: What is the current treatment landscape of PARP inhibitors for patients with breast cancer?
The newest development is the OlympiAD trial and the FDA approval of olaparib for patients with germline BRCA
mutations who have metastatic, HER2-negative breast cancer. The FDA approved use of olaparib in January 2018, so that is available now for patients who have metastatic HER2-negative breast cancer. Those patients also have a germline BRCA1/2
mutation and have seen chemotherapy at some point—either in the initial setting, adjuvant, neoadjuvant, or metastatic setting.
What other PARP inhibitors are being investigated?
Firstly, the OlympiAD trial investigated olaparib compared with nonplatinum standard chemotherapy. Olaparib led to a significant improvement in PFS.
A similar study was presented at the 2017 San Antonio Breast Cancer Symposium using a different PARP inhibitor, talazoparib, in the EMBRACA trial. It was a very similar design with the same population, comparing the PARP inhibitor monotherapy with standard chemotherapy choices. Interestingly, the results were very similar with a significant improvement in PFS by approximately 3 months. It will be interesting to see if a second PARP inhibitor does get FDA approval.
Are there any thoughts of bringing PARP inhibitors to earlier lines of therapy?
Both of the studies I mentioned were for patients who had seen standard chemotherapy—anthracyclines or taxanes—either in the initial or metastatic setting. Now, PARP inhibitors are also being studied in an earlier setting. There are studies, such as OlympiA, looking at [olaparib in] the adjuvant setting for patients with germline BRCA
mutations who have higher risk of disease after they complete standard chemotherapy and local therapy.
Could this benefit patients without BRCA mutations?
That is an important goal we are working on. We want to find patients who do not have germline BRCA
mutations, but whose tumors may be sensitive to PARP inhibitors. The way that investigators are trying to approach that topic is to identify breast cancers that also have the same DNA repair defect as the breast cancers in patients with germline BRCA
-associated breast cancers have a defect in homologous recombination. That is the pathway that repairs double-strand DNA breaks. How can we identify other breast cancers that have this defect? There are various tools being developed. None of them are in clinical use yet, but some of them are interesting. Some look at genomic loss in the tumor, whereas others look at mutational signatures to find those with a defect in homologous recombination. The other approach is to look at patients who either have a germline mutation or whose tumors have a somatic mutation in other genes that work with BRCA1/2
in that DNA repair pathway.
... to read the full story