We presented a phase II study which compared letrozole and palbociclib, which is a CDK4/6 inhibitor, versus chemotherapy as neoadjuvant treatment in luminal breast cancer. The whole purpose of the study was to evaluate the possibility of this kind of combination to in the long term replace chemotherapy in selected luminal breast cancer patients.
Can you tell us more about the patient cohort that went into this trial?
Yes, we selected patients with luminal breast cancer where luminal was defined by the Prosigna test and those patients had to have an ER positive HER2 negative stage 2/3 breast cancer which was not a candidate for breast conserving surgery. So many that have a routine indication for neoadjuvant therapy.
How well was the combination tolerated in terms of comparison to chemotherapy side effects?
As expected but this is the first time that we have a direct comparison between chemo and CDK4/6 plus endocrine treatment combination so the tolerance is excellent. There were virtually no clinically relevant side effects; some neutropenia, of course, but with no clinical incidence. So the combination is extremely well tolerated indeed when compared to chemo.
Were the endpoints in this trial met?
We have two areas of endpoint. The proper endpoint was not met and we have to acknowledge that, because we had chosen an endpoint which is suitable for chemo and probably which is not suitable for endocrine based therapies which is RCB which is a way to define a complete and incomplete pathological response. But when we look at other endpoints which are more adapted to endocrine based therapy or CDK4/6 inhibitor based therapy, that is proliferation measure for example, the PEPI score or the clinical shrinkage of the tumour, the results are absolutely similar and it is absolutely striking.
In terms of the more broadly patient focussed outcomes of progression free survival, overall survival and duration of response, have they been met?
That’s not the point here because this is a neoadjuvant study so the endpoint was focussed on pathological response and clinical response, not on the long term. We will record those data but only as exploratory endpoints.
If, like you say, the only differences between the two are in terms of how the endpoint is measured being tailored more towards chemo rather than for a CDK-based combination what does this mean going forwards?
The first thing is that probably the study, however, paved the way to design larger studies in which we’ll have to design some kind of combined endpoint which would be suitable for both and this is underway.
I think that covers everything, was there anything else you’d like to add?
I guess this is an important study because, again, this is the first time that we in the early setting compared a non-chemo protocol versus chemo. This is of importance because, one, there is still a debate about the real benefit of chemotherapy in luminal breast cancer patients and, two, it is absolutely requested by the community of patients and by our community as well to get rid of chemo in selected patients.