Hope Rugo, MD, FASCO: Thanks very much, Adam. That was really interesting. This is one of the frustrating types of cases that we see—patients who have de novo metastatic disease and have delayed treatment. Although I think that some of the younger patients would have had metastatic disease shortly thereafter anyway because they presented with relatively more aggressive disease. And maybe that’s where we’re seeing an even greater benefit. It’s hard to know with the CDK4/6 inhibitors.
The guidelines are fairly clear that patients with hormone receptor–positive disease should receive hormone therapy in the metastatic setting. But I think for patients who present with de novo metastatic disease or bulky disease or visceral disease, a lot of practitioners are still using chemotherapy as a sort of induction. Ian, what’s your approach to that?
Ian Krop, MD, PhD: I’m always surprised when I hear that. In general, the guidelines—which are based on good data—recommend that we use hormone therapy in all patients with estrogen receptor–positive metastatic disease, except in the cases of visceral crisis or someone you don’t expect to have a good response to endocrine therapy. And a patient with de novo is even more likely to have a good response to endocrine therapy.
Regarding this particular patient, even though she had liver disease, the results of the LFTs [liver function tests] were normal. She had good estrogen receptor and progesterone receptor expression. I think she’s very likely to have a very nice response to the combination of endocrine therapy and the CDK4/6 inhibitor, as Adam suggested. I would think she’s a great candidate for that.
Hope Rugo, MD, FASCO: Adam mentioned that he would choose an aromatase inhibitor [AI] first in this patient population, which is similar to what I’d choose—just liking an all oral regimen rather than an injection until we know that there’s going to be a difference in this patient population. Is that what you do too?
Ian Krop, MD, PhD: I generally use aromatase inhibitors in the first line, unless there is a study that will conclusively show that starting out with fulvestrant is beneficial in the long run. We don’t have that as of yet, and aromatase inhibitors are easier to use. Treatment with these doesn’t require injections. A lot of our other second-line studies are built on fulvestrant, so I think it just makes more sense to use an AI and spare the patient the injections, since they’re likely to be on the treatment for a very long time.
Hope Rugo, MD, FASCO: Also, the combinations in the second-line setting really do use fulvestrant, so that’s important.
Adam, how do you decide which CDK4/6 inhibitor to use in these patients? Is there any difference, for example, in the way you would treat a patient with bone-only disease versus having this limited visceral involvement, or even more extensive visceral involvement that’s asymptomatic?
Adam Brufsky, MD, PhD: Let me address your first question before I go to the second. So in terms of patients with visceral disease that occurs after a number of years—fairly slow growing and estrogen receptor–positive—I would not reach for chemotherapy. I think I would very much agree with Ian. You really need to think about these agents first. Because these have been around for 5 years, I think there really is a movement in our community to do that and not reach for chemotherapy first.
In terms of which agent to use, I think there’s a lot of going back and forth, people thinking that abemaciclib has better validity or at least better data in visceral disease. Again, I think a lot of that has to do with the patient selection on the trials and how they’re measuring the endpoints. I’m not so sure that I agree with any of the data that these agents are much different. I think the biggest difference has to do with the dosage and the toxicities—the diarrhea with one versus the neutropenia with the other two.
For that reason, I don’t have a problem. Since I generally use them for the longest period of time, I tend to use palbociclib. But again, I think if there were data that suggested that abemaciclib were better or ribociclib were better, then I would think about changing. But right now, I tend to reach for palbociclib with the understanding that they’re pretty much the same. I really don’t see much of a difference regarding their efficacy.
Hope Rugo, MD, FASCO: Ian, do you take the same approach?
Ian Krop, MD, PhD: There are patients who have preexisting neutropenia for whom I might favor abemaciclib. For a patient with a brain metastasis that had been treated, I would favor abemaciclib. Obviously, that doesn’t happen very often in this patient population, but it has.
There are some outlier situations when I would favor using abemaciclib first instead of palbociclib, but for most patients I give palbociclib. Given the COVID-19 situation right now—and trying to avoid drugs that cause neutropenia—I am in favor of abemaciclib. In this pandemic situation, we don’t have any data, but it’s something to consider depending on the severity of the COVID-19 virus in your area.
Hope Rugo, MD, FASCO: I think one of the other areas, of course, is the premenopausal patient population. MONALEESA-7 is a really interesting trial. In those patients, I’ve actually been using a bit more ribociclib in an effort to try and use all the agents in all settings, since we don’t really know which one to use when.
Transcript edited for clarity.