Practice Update: Updates on CDK 4/6 Inhibitors in Metastatic Breast Cancer

Director of Saint Luke's Hospital of Kansas City's Koontz Center for Advanced Breast Cancer, Timothy Pluard, M.D., talks with Practice Update about the MONALEESA-2 trial and 4/6 inhibitors in metastatic breast cancer.

Watch Dr. Pluard's interview here, at Practice Update: Updates on CDK 4/6 Inhibitors in Metastatic Breast Cancer.

Dr. Haffizulla: So, Dr. Pluard, you were involved in a very interesting analysis of the MONALEESA-2 trial, looking specifically at tumor response and pain reduction. Can you remind us about the MONALEESA-2 trial and what it was designed to evaluate? 

Dr. Pluard: So, the MONALEESA-2 trial was a first line trial, women…post-menopausal women with hormone receptor-positive breast cancer comparing ribociclib versus placebo in conjunction with an aromatase inhibitor, obviously showing as we all know the significant impact of ribociclib on the progression-free survival, which led to its approval. This analysis was really looking at the objective response and pain reduction, particularly in this population where bony metastases may be a significant issue.

It’s important to know that we’re seeing objective responses, which lead to pain reduction in these patients, because obviously we want symptom improvement as well as disease control. And what we saw was that there was, in those patients who had pain, is significant reduction in pain and clinical benefit from symptom management. So, it’s helpful because oftentimes when physicians are trying to make the decision does a patient…is a good candidate for endocrine therapy or should they go to chemotherapy, we now can say that you’ll get pain reduction with the combination of ribociclib and an aromatase inhibitor.

Dr. Haffizulla: So, you think these results will suggest justifying the use of CDK 4 and 6 inhibitors in this patient population then?

Dr. Pluard: I do. I think it gives us that assurance.

Dr. Haffizulla: Okay. What are some other ongoing maybe unresolved questions surrounding the use of the CDK 4 and 6 inhibitors for the management of breast cancer?

Dr. Pluard: So, they’ve been quite successful in the first line. I feel it’s still an open question. Do all patients need CDK4/6 inhibitors in first line or are there some patients who can still be treated with endocrine therapy alone and reserve the CDK4/6 inhibitors for progression. The unresolved question of whether we should be continuing the CDK4/6 inhibitors beyond progression and changing the endocrine backbone remains unresolved, although we’re starting to see some data which may help us to stratify some interesting data about the molecular mechanisms of resistance was presented today, showing that in some patients it’s RB that is altered and continuing a CDK4/6 inhibitor in that context is probably not going to be effective and changing to a different strategy would be necessary.

In others, it appears that the molecular mechanism of resistance is related more to the endocrine component and so continuing CDK4/6 might make sense in that population, but those are questions we’re going to have to evaluate moving forward.