mBC: CDK4/6 Inhibitor Patient Selection/Sequencing



Hope S. Rugo, MD: We’re going to be faced with having, soon, 3 cyclin-dependent kinase inhibitors that are on the market and available for treatment with patients with metastatic hormone receptor-positive breast cancer. The decisions about which to give to what patient and when are very complicated, and it makes us think a lot about when we had 3 aromatase inhibitors that were on the market and branded and how we decided about using those, which didn’t make a whole lot of sense except for using 1 trial for 1 setting and another for another.

In the first-line metastatic setting, in combination with an aromatase inhibitor, we will have 2 drugs approved: palbociclib and ribociclib. We have them approved today. For abemaciclib, it will be approved in the near future with fulvestrant, and we have palbociclib with fulvestrant. But by next year and certainly the year after, we’re going to have all 3 drugs approved in all indications.

If you just took the way they were studied, I think you could choose either palbociclib or ribociclib in the first-line metastatic setting with an aromatase inhibitor. I think in patients who were taking drugs that interfere with or prolong the QTc interval, I would be much more likely to choose palbociclib than ribociclib. In patients who have any transaminase issues, I’m more likely to choose palbociclib. And patients who can get a blood count check but can’t get an EKG, I would use palbociclib. Otherwise, in patients for whom changing drug doses are hard, getting a new prescription, and you have to get a re-authorization each time you get a new prescription, it may be easier to use ribociclib where you can just tell them to take one less pill and you don’t have to get a whole new prescription. So, that’s another situation. These are all practical issues where the patient assistance might play a role like, “Well, how much patient assistance is available and how many free coupons do you get?” That kind of thing. Otherwise, I would just give one alternating with another really because we don’t know that any one of the agents is better than another, with those caveats in terms of individual toxicity questions and comfort level with the different agents.

Abemaciclib is more different because it’s given continuously. So, I think in a patient who doesn’t have any GI issues with taking medications—and that’s really important, because with GI issues, somebody gets nauseated really easily, has problems with diarrhea already—that wouldn’t be an ideal choice. But for a patient who has a lot of trouble following instructions, taking a drug every single day is always going to be easier than taking it 3 weeks on, 1 week off. And a patient who has problems coming in getting their blood count checked on day 28, who has problems starting the next cycle, coming in for a clinic visit, whatever those issues are, abemaciclib is going to be a great option for those patients.

So, for patients who had previous brain metastases, I would choose abemaciclib right now based on the fact that we have data in the clinical setting—a little tiny bit with abemaciclib, but we don’t for palbociclib and ribociclib. And in the later-line metastatic setting where you might want to give a single agent, you can’t think of a hormone partner that the patient didn’t already receive, I would give abemaciclib based on MONARCH-1. If you think about all the different situations, you can really think about many settings where you might have equivalence or you might see some differences.

Transcript Edited for Clarity

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