DR LOVE: So I want to shift over. We had a bunch of cases presented of ER-positive, HER2-negative metastatic disease. We just talked about early disease. And one of them I thought was very interesting, a 60-year-old patient who presents with a neglected, locally advanced, ulcerating PR-positive, HER2-negative tumor, has a bunch of lesions on CT that are difficult to access for biopsy, look very suspicious for mets. I think it was in soft tissue and bone.

And the question there was what kind of systemic therapy to utilize in the patient. And the audience, the most common answer they gave was endocrine therapy with palbo. But the doc herself brought up the question of giving palbo and exposing patients to the risk of neutropenia with this ulcerating infected lesion. Any thoughts about how you might approach a situation like that?

DR O’SHAUGHNESSY: Hmm. I agree that the standard would be, today, letrozole plus palbociclib. I think that the risk of infection with palbociclib — and now, more recently, with big randomized data from MONALEESA with a very similar agent, ribociclib — the risk of really getting an infection is very, very low. It’s less than 5%. The risk of febrile neutropenia is very low, less than 1%. So we do definitely see some neutropenia. I would monitor the patient’s neutrophil counts carefully during the first 2 months in particular.

But many women, particularly those that are de novo and otherwise healthy, they really don’t have much in the way — they may have some transient Grade 3 neutropenia, but it’s rare to see Grade 4. So I’d just watch the patient very, very closely, certainly get the woman involved in a wound care program, et cetera. But usually she’s close to guaranteed to having an excellent response. And so you can get healing very, very quickly.

I think the issue that I struggle a little bit with, Neil, with the de novo metastatic patient, particularly if the biology is indolent, if the woman gives a history that this locally advanced cancer has been coming on for a great many years and the biology is strongly ER/PR-positive and the Ki-67 is on the lower side, it’s Grade 2.

The question is, does that particular biology, is the best order of treatments to definitely start with the CDK4/6 inhibitor first line, or could the woman just have endocrine therapy, for example, from the FALCON trial, where, in the randomized first-line setting in patients who had had no endocrine therapy whatsoever, the fulvestrant was superior to anastrozole, particularly in those with the soft tissue and bone, the nonvisceral disease. Those with lung and liver metastases had equal efficacy from fulvestrant and anastrozole, but there was a big difference in the bone and soft tissue. And this woman fits into that category.

So I think about that, because we still await survival data from the big first-line randomized Phase IIIs. We will be able to parse this out eventually. I actually was involved with a poster at San Antonio this year in the MONALEESA trial with the letrozole with or without the ribociclib, a very similar agent to palbociclib. And the poster focused on this de novo metastatic population. And indeed there’s a very big difference, improving the progression-free survival even in this de novo population with the CDK4/6 inhibitor added.

So the data — and it’s true as well from the PALOMA series that the de novo patients really benefit very, very much from the CDK4/6 inhibitors. But again, what about these with just the soft tissue and bone disease, not with the visceral, et cetera? But in this particular patient, Neil, she has a very heavy tumor burden, at least in her breast, with a lot of morbidity from this, and so I would be inclined to treat her as most of the adjuvant disease. And I wouldn’t worry too much about infection in her.

DR LOVE: Almost a quarter of the audience said chemotherapy in this situation, maybe prompted by, I don't know, concerns about the locally advanced disease, maybe wanting to get a quick response. I’m sure it would be followed by maybe some hormonal maintenance. What about chemo for a patient like this?

DR O'SHAUGHNESSY: I don’t think that offers any particular benefit. This is a patient that you might want to consider potentially going to a mastectomy strictly from the point of view of local control, if you think that, with soft tissue and bone metastasis, she’s going to live a long time, potentially, from the point of view of metastatic disease. Potentially, a doctor who was interested in chemotherapy may be thinking, “I want to get as much cytoreduction as I can to be able to get this patient to a mastectomy,” just strictly from a local control standpoint, not to affect her overall outcome.

However, I would argue in that situation that either endocrine therapy alone, let’s say, in somebody who had a lot of comorbidities and you weren’t comfortable with a CDK4/6 inhibitor, or in the most cases it would be an aromatase inhibitor with palbociclib. I would argue that your degree of cytoreduction, if you’re patient — you have to wait longer, Neil, but it’s a very high probability of working well for the patient. And if you wait long enough, the patient, I think, will have just as much, potentially, if not more cytoreduction with endocrine therapy than with chemotherapy and particularly with the palbociclib added on. So I actually wouldn’t see a real advantage to the patient with chemotherapy.

Adjuvant and neoadjuvant therapy for HER2-positive breast cancer (BC)

Management of HER2-positive metastatic BC (mBC)

Clinical decision-making for patients with ER-positive early BC

Management of ER-positive, HER2-negative mBC

Indications for BRCA testing in BC and ongoing investigation of PARP inhibition

Treatment of triple-negative BC (TNBC)