The OlympiA trial is a randomised adjuvant trial of olaparib, the PARP inhibitor, against placebo in women with an inherited mutation or pathogenic variant in BRCA1 or BRCA2, the breast/ovarian cancer susceptibility genes, and high-risk newly diagnosed HER2 negative breast cancer. The trial was done internationally and we are now at six years median follow-up.
What was the study design?
This was a 1:1 randomisation for 1,836 individuals with BRCA1 and/or BRCA2 pathogenic variants. They had all of their standard multimodality up-front treatment standard at that time and then they were randomised to a year of olaparib or placebo. The main study endpoint was invasive disease free survival but there were a number of secondary endpoints.
What were the key results?
We had previously reported that there was improvement with olaparib in invasive disease and distant disease free survival, that was at the first pre-specified analysis. At the second we showed overall survival advantage. Now we have 2.6 additional years of follow-up and all of these benefits have been maintained and, importantly, they’ve all been maintained against all subgroups, so against triple negative and oestrogen receptor positive breast cancer and even with various kinds of prior therapy, adjuvant or neoadjuvant, and with BRCA1 or BRCA2.
I should say in addition that the safety profile was maintained, there were very few cases of MDS or AML, four in the olaparib group, six in the placebo group. Then the study also looked this time at second cancer risk.
What is the clinical significance of these results?
The most important thing is that the benefits are maintained, the curves don’t come back together. For a triple negative subgroup this is very stable data. For the hormone receptor positive group we’ll continue to follow, in fact we’ll follow the whole study for five more years, as had been planned, but we’ll have more stable data for them. The second cancer risks are important. Those analyses are a little more complicated because people have preventive surgeries, mastectomies, oophorectomies, during the study so we have to be a little more complex in the analysis if we have the power, fortunately we don’t have a lot of events.
In an exploratory study we showed that pregnancies were similar in the groups and these are young women with BRCA mutations having their cancers, so it’s encouraging that olaparib does not seem in a large way to compromise fertility.
So I’d say that the important thing is that providers should use genetic testing to determine the care of their patients and if they have a pathogenic variant olaparib is standard of care and plays a significant role in the success of treatment.
As we see these days, there are a lot of international trials. I don’t think everyone was optimistic that we would find 1,800 mutation carriers but we certainly did and I think that’s important for other inherited groups and for BRCA carriers and that genetic testing has become part of care and it matters. For that reason, in addition, there is importance to the trial.
