SABCS 2021 | Quality of life results from OlympiA

As you probably know, OlympiA was a very important trial, testing the concept of whether a PARP inhibitor would in fact improve outcomes for women who had residual high risk disease, who were BRCA1 or BRCA2 gene carriers. And the results were presented early because at an interim analysis, the invasive disease-free survival was substantially and significantly approved in those who got one year of olaparib after they had finished their initial treatment for breast cancer with chemotherapy, surgery and radiation if used.

And so because of that finding, we also have done an early analysis of the quality of life data from the trial. Almost all patients had completed collection of quality of life data but not quite. And so since this was unplanned, we’re just doing the protocol specified analysis. But the main concern was whether after patients had received intensive chemotherapy, surgery, radiation, they would have prolonged recovery from that treatment if they took another year of adjuvant therapy with olaparib. And because it’s mostly been used in patients with metastatic disease whose life would be shortened for survivors, this was a very important question. So quality of life assessments were put into the trial, and all of the women who participated, actually there was one or two men who have actually participated, all the people who participated in the trial completed the quality of life questionnaires.

So over 1,800 enrolled patients were actually asked to do this, which is very large for a quality of life study. Normally, we might have 300 or 400 patients in a trial. So the quality of life data is very large compared to the question we wanted to answer. And in some ways, as I present in the meeting, this overpowered for the kinds of questions that we need to answer when patients fill out questionnaires. Nevertheless, we looked at two groups of patients, those who had had neoadjuvant chemotherapy prior to entering the OlympiA trial and those who had received adjuvant chemotherapy, thinking that where they started out when we began either olaparib or placebo might be different. And indeed, we did find that the neoadjuvant patients were a bit more fatigued and had more physical problems than patients who had gotten standard adjuvant therapy. But nevertheless, we had two groups of patients based on the chemotherapy treatment that they had had, and they were each randomized then equivalently to placebo or olaparib. And the main primary hypothesis of the trial was that there might be more fatigue in the patients who had been given olaparib for a year versus those who had been given placebo. And the power for the quality of life study was based on this, and we used the FACIT Fatigue quality of life questionnaire. And primarily, this is a well validated questionnaire. And because this was an international trial, we needed to have a questionnaire that was validated in many languages, so this was why this was chosen.

Through other research that had been done, a meaningful difference between groups for fatigue as measured with the FACIT Fatigue was three points. So the a priori pre-specified endpoint was that if there was three points or greater difference between the two groups, then we would say that there was more fatigue with olaparib. So that was the primary hypothesis.
But we had secondary endpoints that also looked at whether there was more nausea or vomiting or diarrhea with olaparib, and this was measured with the EORTC Quality of Life Core Questionnaire. And we also looked at global health and quality of life with the EORTC, as well as physical functioning and emotional functioning. And again, the hypothesis here was that there would be a good recovery in terms of those global dimensions of functioning for women in both groups, that there would not be any impairment with olaparib, but we were concerned that there might be some GI symptoms. And we again were, secondary endpoints, looking at nausea and vomiting as well as diarrhea.

So that was how the trial was set up and we looked at both groups. And the main endpoints were really for fatigue at six and 12 months during treatment with olaparib or placebo. And what we found was there was a slight increase, statistical increase in fatigue, one point, one and a half points between the two groups, but it did not meet the three point clinically meaningful endpoint. So we can say that there was no excess fatigue associated with one year of olaparib. In the secondary endpoints, however, we did see an increase in nausea and vomiting, single item question for that, and that was more significant with olaparib. And again, that’s consistent with what was reported in the toxicity ratings from the main trial that was reported in the New England Journal. So it would be most unusual if patients didn’t report what the clinicians had reported. So that’s good to see that.

Importantly, fatigue and nausea and vomiting and all of the other symptoms that we looked at and functioning improved in the subsequent year when there was no treatment being given, and both groups looked very similar. So the conclusion is that the one year of olaparib therapy did not meaningly interfere with fatigue and energy in women taking this treatment. And overall, there was recovery of women over the two years after adjuvant therapy ended.