Sara M. Tolaney, MD, MPH: The CDK4/6 inhibitors—some of them can come from your local pharmacy, some can come from a specialty pharmacy, and it’s really very much insurance dependent for how it’s going to get dispensed. I’ll say I don’t usually know this ahead of time, so what I do is I prescribe the drug, and I tell the patient that I sent the prescription to our pharmacy. Then in our system we have a plan in place that it gets reviewed by our pharmacy to know how the drug could get dispensed. And then that gets communicated back to us to let us know whether they were able to dispense or if it had to get sent out to the specialty pharmacy.
And I think that communication piece, again, is critical because the patient then needs to know how they’re going to get their drug and then when to expect it. And so it is really just dose dependent on each person’s plan with each different drug. It isn’t something that we usually keep track of. I will say when it comes from a specialty pharmacy, it does create a little bit of a delay because then it has to get sent from the specialty pharmacy to the patient, as opposed to them just picking it up the same day I prescribed it at our pharmacy. So that, again, has to be taken into account when scheduling monitoring for the patient and follow-up.
Lindsay Shaw, NP: I think we rely on our nursing staff to communicate with them to overcome that barrier of not seeing them so frequently. And we have a great team of program nurses that help us do that. In the beginning as well. I mean, we are seeing them every 2 weeks, which is not terribly different from any other schedule. So when they’re initiating therapy, we are keeping a close eye on them and talking to them every few weeks face-to-face. And I think, again, it’s about setting expectations. A lot of these patients haven’t been coming to the clinic very frequently before starting this, and it is new. So when there’s been a change, they like to see us more frequently, and, you know, questions come up as time goes on. And so those few visits that are clustered in the beginning can be really helpful to get them to understand what to expect.
Sara M. Tolaney, MD, MPH: Certainly one of the challenges with CDK4/6 inhibitors as opposed to just giving endocrine therapy alone is that they do require more monitoring than we certainly had been doing with endocrine treatment by itself. So specifically for all 3 agents, we do need to monitor the CBC [complete blood count] with differential on day 1. So cycle 1, day 1; cycle 1, day 15; cycle 2, day 1; cycle 2, day 15; and then we start our new cycle, cycle 3.
Thereafter, usually the monitoring can get loosened up to every 2-ish per month as people go depending on what adverse effects they may have experienced. There are slightly different monitoring requirements for each agent. And so specifically for abemaciclib and ribociclib, one must also monitor liver function tests. So that must also be done every 2 weeks for the first 2 months. And then specifically for ribociclib, one must also monitor QTc [corrected QT interval], and so one must get an EKG [electrocardiogram] on cycle 1, day 1; cycle 1, day 15; and cycle 2, day 1. And that’s really looking for any prolongation in the QTc, which is associated potentially with ribociclib.
So with all 3 agents, again, there really is some form of monitoring every 2 weeks for the first 2 months. I think the only other warning that one has to keep in mind that’s a little unique is that abemaciclib has been associated with a slightly increased risk of developing a venous thromboembolism. So that is something to keep in mind. And certainly all our patients with metastatic breast cancer are at higher risk for developing a clot. But it seemed like it was at a slightly higher rate than we would have seen just with a patient with metastatic disease.
Lindsay Shaw, NP: All 3 drugs cause fatigue, and I always counsel patients that they will probably experience some fatigue, though not so much that they won’t be able to live their life pretty normally. There are exceptions to that. There are some patients who have grade 3 or rarely grade 4 fatigue, but I always tell people there’s always the option for a dose reduction. And one of the exciting things that Sara mentioned was with abemaciclib, when dose-reduced for diarrhea, which is separate, but that there wasn’t a difference in disease in progression-free survival, which I think we can’t always tell people. People always have that question with any therapy.
In terms of diarrhea management, with abemaciclib in particular, I tell people, chances are you will get this. There’s a small percentage of patients who don’t get diarrhea, but once we know how bad your diarrhea will be, we can titrate the loperamide dosing to control it. I think we’re 95% or more successful in managing adverse effects overall to make these drugs tolerable and allow people to live their life as close to normal as they can.
Sara M. Tolaney, MD, MPH: And I think also we certainly do see issues with neutropenia, with palbociclib and ribociclib. You know, about 60% of patients end up needing dose holds or dose reductions. But you know, that’s all very manageable. And as Lindsay was saying, the first 2 months are really a time when we’re sort of feeling out how they’re going to tolerate it, and once they usually pass that, we’ve usually done our dose hold and dose modification. And so usually they’re on a pretty stable dose thereafter and, again, are usually pretty manageable.
I think it is also important to note that although these drugs do cause a lot of neutropenia, it’s very rare that they cause infectious complications. So there’s only about a 1% to 2% rate of febrile neutropenia with these agents. This is very different from what we see with chemotherapy. So again, usually this is something that can be well managed without serious complications.
Again, the only other thing that we sometimes see is some elevation in liver enzymes, which, again, is usually pretty mild and not something that I’m usually having to do dose holds and dose reductions for. And then finally I think the issue regarding QTc monitoring with ribociclib: I think it’s important to keep in mind if you’re giving other agents, too, that may be prolonging QTc simultaneously, and so that is a little complicated. You have to just be mindful of what agents that patient may also be on.
Lindsay Shaw, NP: So generally with our patients, we usually like to see them every 2 weeks for the first 2 months if we can, if they don’t live a far distance from us. Because they would be coming in for a lab check anyway, we usually will see them to assess what adverse effects they’ve had and see whether they need any dose holds or dose reductions during that timeframe. So that’s either with Lindsay or me for, again, those first 2 months.
Thereafter, their patients are often seeing us every couple of months. It also depends how they seem to be responding to therapy. And if we see that they’re tolerating treatment well and aren’t having new symptoms from their underlying disease, certainly those visits can get spaced out, and we usually like to time them with time points also of restaging scans along the way.
You know, many of these patients also need bone-modifying agents. And whether it’s zoledronic acid or denosumab…some of these patients are coming in either monthly or every 3 months depending on what agent they’re getting for those treatments in addition. And so if they’re coming in for those treatments, we’ll often see them in conjunction with that too.