EMBRACA was an open-label, randomised international trial looking at talazoparib, which is a once-daily orally dosed PARP inhibitor versus physician’s choice of chemotherapy in women with metastatic breast cancer that have also a BRCA1 or BRCA2 germline mutation.
When it came to comparison to physician’s choice, were there any criteria that it had to meet?
The patients had to have a breast cancer that was not HER2 positive, it was stratified on tissue receptors as well as whether or not they had central nervous system metastases and the lines of prior therapy.
The primary endpoint was progression free survival by a central blinded review, and with a little over 11 months of median follow-up there was an improvement in progression free survival with a hazard ratio of 0.54 that was statistically significant. We also had a pre-planned overall survival interim analysis that is showing a hazard ratio that is favouring talazoparib at this time, but there’s only 51% of the events at this time and so the data is immature, it has not reached statistical significance. As we look at the curve we notice a significant tail that comes at the end of the curve and there is a significantly higher percentage of patients that are still ongoing on the trial on talazoparib at this time versus physician’s choice, as well as more patients in the overall survival follow-up.
What I think also was very intriguing about this study was the quality of life. What we saw was that patients who received talazoparib actually had an improvement in their quality of life versus those patients on physician’s choice therapy that actually had a deterioration, and there was a statistically significant difference between these two groups. I think that we need to continue to follow this overall survival curve, it is the largest of the BRCA positive metastatic PARP trials, and it is powered to look at overall survival, so we will need to follow that as the data matures.
The improvements in quality of life that you saw, was that related to any specific toxic events that were or weren’t happening?
What we did notice for toxicity, which was a little bit different, was anaemia was the most common side effect that we saw in talazoparib. It was most often managed with holding the dose, dose reductions and some blood transfusions. I think it’s important to note that only two of the patients on the trial had to come off of the study because of anaemia that was not able to be managed. Otherwise, all of the side effects seemed to be fairly balanced, except for there was more diarrhoea and hand foot syndrome which we do account to the capecitabine which most patients were on for the physician’s choice therapy. We did also see alopecia on talazoparib; the vast majority was grade 1, versus a higher rate of grade 2 in the physician’s choice.
Do you see this working towards possible combinations which have this improved quality of life limiting some of the toxic events that you see with other treatments?
The alopecia was seen with a single agent, and it is an oral daily dosing, so I don’t think a cooling cap would come into play there. I do think the future of research at this point for these PARP inhibitors, we certainly see a lot of sensitivity, and the time to response was, in my experience treating patients with PARP inhibitors, very similar, if not sometimes it appeared to me quicker than chemotherapy. Right now outside of our single agent we’re not seeing the same type of activity for patients who don’t have the BRCA mutation, so the future combinations to try to expand the patients that might benefit from PARP inhibitor, including immuno-oncology agents and other DNA damage repair agent combinations, are where we’re going next. We also have trials looking at this agent in early, pre-operative neoadjuvant setting for patients with operable breast cancer.