The MONALEESA-7 trial is one of several trials that has tested a new class of drugs known as cyclin dependent kinase inhibitors when combined with endocrine therapy for patients with metastatic breast cancer that’s hormone receptor positive and HER2 negative that these generally double progression free survival. Three CDK inhibitors are now approved for use either in first or second line therapy.
The MONALEESA-7 was the first study that looked at this specifically in premenopausal patients. Premenopausal patients are typically treated with suppression of the ovaries to prevent production of oestrogen and otherwise with the same therapies that we use for postmenopausal patients. The MONALEESA-7 initial results have already been presented and published and in this patient population the CDK inhibitor ribociclib significantly prolonged progression free survival, roughly doubled it, as the others had. This particular report that is being presented at ASCO looked at the survival benefit because so far none of the CDK inhibitors have actually extended survival.
The survival analysis of the MONALEESA-7 trial did in fact show a survival benefit that was strongly statistically significant. This is really an important landmark in that it’s the first time that a CDK inhibitor is found to be actually extending survival. The other findings of this study were what is called PFS2, that is progression free survival not only for the trial period but for the treatment that they got next. When you add those two together it still extends survival because sometimes we’re concerned that when patients become resistant to a drug that they may actually have a shortened, very shortened, response to the next therapy and we did not find that to be the case.
No new safety signals arose either so, in summary, this is an important finding. It shows a survival benefit. We can’t explain exactly why we’re seeing this in this trial and not in the other trials at this point. It could be the younger population, it could be a difference between the drugs, but that’s going to require further exploration.
The important thing about these results is that we are seeing a survival benefit from this class of drugs and that’s probably the most important message. Secondarily, what we don’t know yet is whether this drug should be preferentially used for patients in general or that are premenopausal. I think that’s going to take some further consideration and deliberation. This is usually something that is debated on a wider scale amongst experts and consensus panels are assembled to see if this should actually change recommendations. But that process will be ongoing and, in the meantime, we do know that we’re at least on the right track. We’re very interested in analysing further the tissue and blood specimens from this trial. We have reported some preliminary analysis but now we can focus on those alterations which may be correlated with improved survival. That may help us pinpoint some new directions for research.
Why is it important to focus specifically on premenopausal women?
Premenopausal patients have generally been treated with ovarian suppression and then some of the same endocrine therapies that we have used, particularly some of the newer generation hormonal therapies like aromatase inhibitors and fulvestrant. However, with the new biological therapies, particularly with the cyclin dependant kinase inhibitors, we could not just assume that we could use ovarian blockade and felt that we had to have a dedicated clinical trial. This is the only one of its kind. It’s large enough for us to be able to look at different subsets of patients and be confident that we can actually achieve this. So we were actually pleasantly surprised, I must say, when we saw the survival benefit results. But it is important to be able to study populations of specific interest when one can do so with a specific trial. This also applies to older patients because they have generally been underrepresented in many of our clinical trials.