Medicine Matters oncology

The OlympiA trial was a long time coming. It is a study of whether the addition of olaparib, a PARP inhibitor, can improve outcome for women with high-risk breast cancer, either triple negative or ER positive, both HER2 negative and a BRCA1 or BRCA2 mutation in their germline-- so the inherited version in this study, not in the tumor.

Over 1,800 women from around the world-- this was a cooperative study between the BIG, the NRG in the US, and AstraZeneca/Merck, our industry partners.

And in this study, these women with their BRCA1 or 2 mutations had high-risk breast cancer. So that meant that they either had sufficient disease at diagnosis to be considered high risk, especially triple-negative breast cancer. But if they had ER positive disease, they had to have a lot of disease, four or more positive lymph nodes.

Women received all of their upfront treatment, so their local therapy, surgical radiation, if that was given, and either adjuvant chemotherapy or neoadjuvant chemotherapy. But in this study if they had neoadjuvant therapy, they had to have persistent disease at the end, and they could not receive additional chemotherapy. They were then randomized to receive one year of olaparib or placebo.

So this study was scheduled to report out later, but the data safety monitoring committee stopped when a prespecified endpoint was reached and felt that the result was so stable that we would not be at risk of having a reversal, for example, of the findings.

And what this study showed was that compared to placebo, patients receiving olaparib had a 42% reduction in local recurrence, in metastatic recurrence, in death due to any cause but particularly breast cancer, and other new cancer. So the invasive-disease-free survival was longer with olaparib, and it was with a hazard ratio of 0.58 and a p-value of 0.0001. The difference was 8.8%.

So I want to emphasize that at this time in this short period of follow up, only 2.5 years median follow up, we do not have a statistically significant overall survival advantage. We have a mathematical difference, but this is not statistically significant at this time. And this is important because of the way that you have to share p-values when you look at a study at different time points during its evolution. So we cannot yet say that there is an overall survival advantage.

So what does this mean? Well, we hope that what this means is that for women with BRCA1 and 2 mutations who are found to have significant breast cancer-- and often this will be women who may not have realized they had that mutation until they were diagnosed, which means that genetic testing has to be available to our patients who have either triple-negative or ER positive HER2 negative disease and may have a mutation. And, of course, we can't always predict that by family history.

So we hope that testing will be available because for these women, the addition of a year of olaparib after completion of their upfront therapy can offer a benefit at least in invasive-disease-free recurrence. And we hope that will translate into more, but, of course, we don't know that at this time.

Because the study was conducted worldwide, we're comfortable that this is a true finding for all population groups. And we are excited to see what the future will bring with other progress in breast cancer and how this will fit in. But for this patient population, we now have something to offer beyond standard therapy. And for our triple-negative patients in particular, that's very important. Perhaps I should mention that ER-positive patients, of course, did receive adjuvant hormonal therapy throughout the study with olaparib as well.

The OlympiA trial was an unusual study in its structure because of the collaboration between the international academic community and AstraZeneca/Merck. One of our principal investigators, a cochair of the study, Dr. Bella Kaufman, passed away before the study results could be made public. But she was aware of them, and she made a huge contribution. We'd like to acknowledge her.