PARP Inhibitor Staves Off Recurrence in Early BRCA-Mutant Breast Cancer

The addition of olaparib (Lynparza) to standard treatment significantly improved disease-free survival in patients with early, high-risk HER2-negative breast cancer and germline BRCA mutations, according to results from a phase III study reported at the virtual American Society of Clinical Oncology annual meeting.

In this exclusive MedPage Today video, Amy Tiersten, MD, of Mount Sinai Hospital in New York City, offers her takeaways from the OlympiA study.

Following is a transcript of her remarks:

This is a really exciting study, it’s an 1,800-patient trial for early-stage breast cancer in patients who have a BRCA1/2 mutation. Showing that a year of one of the PARP inhibitors, namely olaparib, significantly reduces the risk of recurrence.

Olaparib has already been FDA approved for metastatic breast cancer, and it’s also used to reduce the risk of recurrence in ovarian cancer. But this is the very first adjuvant PARP inhibitor trial for early-stage breast cancer. So it’s always exciting to see a drug that we use in metastatic disease move into the earlier setting, where we’re actually curing more patients.

Some of the interesting things about the study: about 80% or so of the patients were triple-negative — so these were patients who are either ER-positive or triple-negative. HER2-positive patients were excluded. So it’s extra exciting for this group of patients with whom we currently have no targeted therapy to give after chemotherapy.

Just by way of review, PARP inhibitors are oral targeted therapies that interfere with the cell’s ability to repair DNA damage. And that is, BRCA mutated cells already have difficulty repairing DNA damage, which makes PARP inhibitors particularly effective in that group of patients.

In this trial, about 1,800 patients were randomly assigned after completing adjuvant chemotherapy to either 1 year of the olaparib versus placebo. And what we found was a 42% improvement in invasive disease-free survival, namely at 3 years, the invasive disease-free survival went from 77% to 86% with the PARP inhibitor, and distant disease-free survival improved from 80% to 86%, which represents a 43% [relative] improvement. So very, very exciting.

The toxicities were very manageable. There was actually no difference in serious adverse events among the olaparib versus the placebo group. There were more mild and manageable blood count issues as would be expected in the olaparib group. Patients were eligible if they had particular eligibility criteria that pick out the highest-risk patients.

And the study just really underscores the exciting revolution in targeted therapies and the ability to move these drugs into earlier-stage disease. The study really underscores the need to do a genetic testing for all of our breast cancer patients at this time, so we can make sure that we’re making these drugs available to all the patients who might benefit.