DR HURVITZ: We currently have a neoadjuvant clinical trial ongoing called neoMONARCH that we’ll be presenting at ESMO, which is kind of an interesting trial design. It’s basically a biomarker study, so ER-positive, HER2-negative postmenopausal patients with a breast tumor of at least a centimeter in size. And they are assigned to receive 2 weeks of abemaciclib plus anastrozole, or 2 weeks of anastrozole, or 2 weeks of abemaciclib with a biopsy at day 1 and 14. And then after day 14, all patients receive both drugs for the completion of 4 months and then go to surgery.

And our endpoint is looking at change in Ki-67. And we’re going to be exploring a lot of things — Phospho-Rb and that whole pathway and just trying to understand if there are markers of response or resistance to this therapy. So I think there’s going to be a lot more data coming out, especially with biomarker-rich information to be provided.

DR LOVE: Yes. And I think until that comes out, it’s maybe not going to be too clear what the future of monotherapy is. But the bottom line is, I mean, I’ve heard people who’ve been involved with these trials. I say, “Have you had any patients who had useful responses to abemaciclib alone, the patient benefited, it lasted a while?” And I’ve heard about cases like that. Have you had any cases like that?

DR HURVITZ: I haven’t yet, because I wasn’t participating in those early studies. But I have heard from colleagues and steering committees about very substantial responses that they’re seeing in their patients.

DR LOVE: And what about the neoadjuvant study, the neoMONARCH? How many people have been treated so far? And is it blinded, or do you know what they’re getting?

DR HURVITZ: It’s open label. It’s Phase II, so we do know what people are receiving. And we have — gosh, we’re about 70% enrolled. And our goal is just over 200 patients. It’s an international trial. And what I’ve seen is a drop in Ki-67 from day 1 to day 14, which should be predictive of longer-term outcome for patients if you follow the data in this setting.

DR LOVE: What about actual tumor shrinkage neoadjuvantly?

DR HURVITZ: The patients I’ve put on are just beginning to go to surgery now. But clinically, we’re seeing remarkable softening of the tumor, becoming difficult to palpate, disappearance of lymph nodes by examination. But we’ll have to see what the actual data shows. We’re going to present it, the biomarker data, at ESMO and then hopefully have some clinical pathologic response data at San Antonio.

DR LOVE: That’ll be really interesting to see. I kind of have been hearing that still, like, maybe the future of abemaciclib is still going to be combined with hormonal therapy. Is that your take?

DR HURVITZ: I think so. I mean, I think that’s the direction things are moving. While their data is very exciting, they’re late in the game. So I think from a company perspective, they’re going to have to do what gives them the highest odds of yielding good responses.

And I also think that these companies that are later in the game, ribociclib and abemaciclib, have got to be brave and look at other areas — for example, HER2-positive, which our laboratory — the work that we’ve done in looking at these molecules indicates that hitting the CDK4/6 pathway should be very effective in HER2-positive tumors. Not all HER2-positive tumors, but there’s a lot of sensitivity there. It’s a crowded field, so I think companies are a bit reluctant to go into that realm. But I think we’re going to see some studies evaluating that.

Genomic assays and (neo)adjuvant treatment decision-making

Early-stage breast cancer in the adjuvant and neoadjuvant settings

Management of metastatic breast cancer (mBC)

CDK4/6 inhibitors for the treatment of breast cancer

Checkpoint inhibitors and other novel immunotherapeutic approaches to breast cancer

Triple-negative and BRCA mutation-positive breast cancers