The purpose of this trial, of this subgroup analysis, really was driven by this curiosity that I think a lot of the data for adjuvant CDK4/6 inhibitors has sort of sparked. And that’s really, now that we have this new class of drugs, it seems to clearly be effective in intermediate and high-risk ER-positive HER2-negative breast cancer in the early stage setting, to what degree do we still need chemotherapy? So these drugs work...
The purpose of this trial, of this subgroup analysis, really was driven by this curiosity that I think a lot of the data for adjuvant CDK4/6 inhibitors has sort of sparked. And that’s really, now that we have this new class of drugs, it seems to clearly be effective in intermediate and high-risk ER-positive HER2-negative breast cancer in the early stage setting, to what degree do we still need chemotherapy? So these drugs work. We just presented the five-year outcomes of MONALEESA showing that there’s still continued benefit beyond stopping after three years. And so now that we have this new class of drugs, the chemotherapy that people still receive as part of standard of care, how important is that? Is there any way we can sort of not need to use that? Now, obviously, MONALEESA was not designed to answer that question. So everyone who got chemotherapy on the MONALEESA trial received it as part of standard of care prior to enrolling on the trial. So they either got it as standard of care in the neoadjuvant setting if their doctor felt that that was the right thing to do, or they got it as adjuvant therapy. But either way, it was prior to enrolling. And so what we decided to do was look at a subgroup of patients who we have looked at before. We’ve looked at the neoadjuvant patients on MONALEESA as a whole. And as a whole, the neoadjuvant patients did better with ribociclib as compared to the control arm, which is essentially what we see with all subgroups. All the subgroups so far seem to do better with the addition of ribociclib. But what we looked at was really a different question. We looked at which patients who received neoadjuvant chemotherapy had an objective response to that chemotherapy. So basically, if you got chemotherapy, did the tumor shrink? Did the nodes go from node positive to node negative? Was there a drop in the Ki-67? Some kind of objective response prior to getting chemo and then after getting chemo. And so based on that, we categorized patients as either having a chemo response or they’re a chemo responder or they didn’t respond to chemotherapy. And so those were the two sort of groups that we were looking at. And then separately within those, we looked at those in the control arm and then with the addition of ribociclib. And what we found was very interesting. So in patients who had received only, who had gone on to receive only standard of care endocrine therapy, which is a non-steroidal aromatase inhibitor, with or without goserelin if they’re premenopausal or men. Essentially, those patients, if they had a response to chemotherapy, they did better than patients who didn’t have a response to chemotherapy. They had an improved invasive disease-free survival. So basically, if you responded to chemo, you did better than patients who didn’t respond to chemo. And that sort of makes sense, right? We would expect that to make sense. We would probably expect that finding. However, when we looked at it in the ribociclib population, there was no statistical difference between the two groups, showing that that benefit that you saw with chemotherapy without ribociclib, that benefit no longer was detectable once you added in ribociclib. So it’s a very interesting finding. I think what it represents is you’re placing a drug that is within the pathway between response to chemotherapy and invasive disease-free survival. So I think this is hypothesis generating. It’s very interesting data. And it seems to suggest that adding ribociclib on top of chemotherapy, the response to chemotherapy doesn’t sort of play as much of a role anymore once everyone’s receiving ribociclib. But without ribociclib, that’s not the story at all. There’s a clear benefit that’s detectable from chemotherapy. So to me, this is very hypothesis generating and would warrant further study of using CDK4/6 inhibitors, in some cases maybe without chemotherapy and sort of sparing some patients chemotherapy who would have otherwise been eligible for it.
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