Medical experts discuss strategies to optimize treatment adherence for patients diagnosed with breast cancer.
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: Adverse events, we’ve highlighted a lot of these throughout our discussion. We talked about neutropenia, rare febrile neutropenia. We’ve talked about some of the GI [gastrointestinal] adverse effects around diarrhea. Before this panel we were discussing, do you start certain CDK [cyclin-dependent kinase] 4/6 inhibitors at a lower dose, see how patients tolerate it, and then ramp up the dose, or start high and then go lower? [Dr Sammons], walk me through that, [among palbociclib, ribociclib, and abemaciclib,] although they’re not yet approved in that early patient, among them, what would be concerning? I know [Dr Andersen], for example, brought up QT prolongation, but what would you be most concerned about if you were trying to tailor therapy to a patient or if you do have a patient on something that you try to monitor for among the 3?
Sarah Sammons, MD: I think definitely in the metastatic setting and now in the early-stage setting, I’ll soon be prescribing more ribociclib and abemaciclib. Of course, neutropenia is more prevalent with palbociclib and ribociclib. We are all very comfortable managing that now with dose reductions. What I tell patients is, this is asymptomatic neutropenia. Even though your counts on paper are not going to look very good, your risk of a severe infection is extremely low, and in the clinical trials less than 1%. So we manage that with dose reductions very well. For the ribociclib and abemaciclib, liver toxicity is something [for which] we definitely have to monitor their LFTs [liver function tests] and manage that accordingly, bringing it into the early-stage space. I think that’s important. Diarrhea with abemaciclib is very manageable with dose reductions and modifications with supportive medications. Right now, we’re not in a place where we’re dose escalating or starting at lower doses, but my institution is starting a trial to look at that in the adjuvant setting with abemaciclib. Could dose escalation and aggressive supportive management up front be helpful? I think it’s important to think about in the adjuvant setting, what are the adverse effects that we can’t manage with a dose reduction or a modification? With adjuvant abemaciclib, the risk of blood clots in the all-comer population was around 3%. That’s something that we have to think about. And something that I also like to bring up is that the risk of blood clots when tamoxifen was given with abemaciclib in that trial was much higher. If you give it with an aromatase inhibitor, it was about 1.5%. So I do not prescribe it in the adjuvant setting with tamoxifen. In fact, NATALEE does not allow tamoxifen. The NATALEE trial [NCT03701334] requires all patients to be on an aromatase inhibitor. And all premenopausal women in NATALEE had to be on a GnRH [gonadotropin-releasing hormone] analog. There are also small risks of pneumonitis, which is something with all of the new drugs in breast cancer we’re managing more and more, but there certainly is a risk of pneumonitis that’s smaller in patients getting adjuvant radiation, something that we have to be aware of.
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: How often would you say you’re monitoring patients, whether it’s with labs or…getting a baseline [electrocardiogram] for…your patients? Are they coming in when they start, is it every 2 weeks, every month? How does that look in your practice?
Sarah Sammons, MD: I go by the guidelines. I am a guideline type of gal. Right now for abemaciclib, we see them at baseline; there’s no need for a mandated [electrocardiogram] with abemaciclib. We see them with labs every 2 weeks for about 2 months and then monthly after that. We can space it out once they’re on a dose that you’re comfortable with.
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: Got it. Are there any different monitoring parameters from our panelists?
Jay Andersen, MD: I’ll point out that fatigue is an issue sometimes. And that’s quality of life, certainly in both settings, that sometimes warrants a dose reduction, but I’ve seen patients who dramatically respond to the dose reduction and feel much better.
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: Got it.
Sarah Sammons, MD: I agree.
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: We’re obviously talking about oral therapies, adherence, and compliance. We’ve talked a little bit about dispensing and pharmacy services and all these different kinds of things, but [Dr McArthur], hearing from you and your experience and practice, are there any things that you do that are in place to help promote adherence and compliance to treatment? Are you finding that there are challenges with adherence and compliance? I would think that in this patient population with curative intent disease, that plays a critical role. Are you doing anything special? I’ve seen it all over the place with different strategies. I’ve seen calendars, phone reminders, and the use of digital technology to try to report back to us how patients are taking their oral oncolytics. What are you doing?
Heather McArthur, MD: I’m somewhat privileged in that I’m in an academic environment, and I spend quite a bit of time on that initial new visit educating the patient, orienting them, conveying ideas about what we’re going to do immediately vs long term. And this is typically a very motivated patient population. They’re at extremely high risk for recurrence. That investment of time up front really pays off because it engages the patient in the process and gives them the long-term view of what to expect over months and years to come. And then whenever there’s a change in therapy, when I’m starting them on hormone therapy, for example, we’ll again revisit all of those ideas because I know that at that new visit, they only heard 30% of what I said at that time. I have to revisit that information, but at least I laid the groundwork up front, and then I can always revisit patient education and talk about data. They understand that a more than 6% improvement in cure rate with the addition of adjuvant abemaciclib, for example, is a meaningful benefit, and they tend to be [adherent] as a result. In terms of just practical strategies, I typically wait several weeks after radiation is completed, if radiation is indicated, so that they can recover from often-delayed radiation-related adverse effects before I initiate hormone therapy. Typically, [in] our highest-risk population, so a premenopausal patient who requires ovarian suppression, an aromatase inhibitor, and a CDK4/6 inhibitor, I incorporate those drugs in a stepwise fashion to build confidence. So, I’ll start with ovarian suppression, in the next month I’ll add in the aromatase inhibitor, and the following month I’ll add in the CDK4/6 inhibitor. It allows me to tease out [whether] there’s going to be a toxicity issue and which drug is contributing to the toxicity, and it also builds confidence with patients, which they appreciate.
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: Got it. Are there any different experiences around adherence and compliance, or is anybody doing anything out of the box?
Samyukta Mullangi, MD, MBA: I like that approach.
Jay Andersen, MD: No, I like that. I do that frequently too. I parse it out, especially if I’m adding Zometa [zoledronic acid] as well. I’ll strategize the schedule. But I think it’s critical. I think in the first 2 months, when we’re monitoring the labs, is when we’re going to see most of the toxicity issues. I think just having that regular follow-up is helpful.
Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: Yes, and I think they coast, once you’ve found the happy dose or happy supportive cares, [and] they become more self-sufficient.
Transcript edited for clarity.