In this episode, experts discuss practical, patient-centered strategies for CDK4/6 inhibitor therapy in HR-positive/HER2-negative breast cancer, with a focus on adverse event monitoring and management, dose modifications, adherence support, and preventing early discontinuation. The discussion also highlights real-world approaches to counseling, multidisciplinary coordination, and helping patients stay on therapy long term.
In this episode, Danielle Roman, PharmD, BCOP, and Jordan Hill, PharmD, BCOP, discuss patient-centered management of CDK4/6 inhibitor therapy in HR-positive/HER2-negative breast cancer, with a focus on how oncology pharmacists and the multidisciplinary care team can support patients through treatment, including:
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Presenters:
Danielle Roman, PharmD, BCOP
Manager, Oncology Clinical Pharmacy Services
Oncology Clinical Pharmacy Specialist
Allegheny Health Network
Pittsburgh, Pennsylvania
Jordan Hill, PharmD, BCOP
Clinical Pharmacy Specialist, Breast Oncology
West Virginia University Cancer Institute
Morgantown, West Virginia
Link to full program:
https://bit.ly/4cIYca6
This transcript was automatically generated from the audio recording and may contain inaccuracies, including errors or typographical mistakes.
Patient-Centered Management of CDK4/6 Inhibitor Therapy: Adverse Event Mitigation, Adherence, and Persistence in HR+/HER2- Breast Cancer
Introduction
Danielle Roman: Thanks for joining me for this Decera Clinical Education podcast on patient-centered management of CDK4/6 inhibitor therapy for hormone receptor-positive, HER2-negative breast cancer. I am Danielle Roman. I am a clinical pharmacy manager and clinical pharmacy specialist at Allegheny Health Network in Pittsburgh, Pennsylvania. I am joined by my colleague Jordan Hill. Jordan, I will let you introduce yourself.
Jordan Hill: Hi. Thanks for joining us. I am Jordan Hill. I am a clinical oncology pharmacist at the West Virginia University Cancer Institute in Morgantown, West Virginia. Happy to be a part of this discussion today.
Danielle Roman: We are here today to discuss some of our experience with managing CDK4/6 inhibitor therapy. We are going to talk about all of our three CDK4/6 inhibitors today, but really focusing in on the two that we are using in the early-stage breast setting now, ribociclib and abemaciclib. We are going to first kick off with some discussion of toxicity profile management strategies. These drugs are certainly not benign. There is a lot to talk about here. A lot of unique toxicities that we can see with these agents.
[00:01:35]
Key AEs With CDK4/6 Inhibitors: Monitoring and Preventing
We will kick it off there. I would like to highlight that as we use these agents, early identification of toxicities is incredibly important. We have a lot of structured management strategies that we can utilize if we know about the toxicities. Really close monitoring is incredibly important and something I think you will see as a focus as we go through these slides.
We will first start with just an overall discussion of some of the key adverse effects that we are monitoring and managing with this drug class. A couple of the key ones to highlight. Diarrhea is something that we can see with all of these agents, although it is one that we see more so with abemaciclib. That is a toxicity that we will be highlighting further as we continue in our discussion. Hepatobiliary toxicity is another one, an important one with abemaciclib and ribociclib. We see it much less so with palbociclib. Neutropenia is another one we will be spending some time on. Something we can see across the board with all three, abemaciclib, ribociclib, and palbociclib and requires strict monitoring strategies.
A mention of VTE is something that is in the prescribing information as a warning with abemaciclib. It should be a counseling point for patients receiving abemaciclib. ILD or pneumonitis. There is an FDA warning that came out with this drug class. All three of our agents, we should be monitoring for changes in pulmonary status that may indicate ILD or pneumonitis. Things like hypoxia, cough, dyspnea. It is an uncommon toxicity but certainly one that should be on our radar with these drugs. Then finally we will have some discussion on QTc prolongation, specifically something we see with ribociclib.
[00:03:36]
Key Differences With Abemaciclib, Palbociclib and Ribociclib
Now, in terms of the toxicity profiles with these agents and we mentioned abemaciclib diarrhea is a very common toxicity. It is usually the toxicity that we think about when we think about this agent. Early use of loperamide, hydration, dietary modifications are very important. With ribociclib, QTc prolongation and increases in LFTs are important monitoring points. We can also see increases in LFTs with abemaciclib. Then I mentioned the hematologic toxicity is something that we can see as a class effect with all of these agents. Palbociclib and ribociclib do tend to have more of the neutropenia effects compared to abemaciclib, which tends to be less severe.
[00:04:24]
Monitoring and Managing CDK4/6i-Induced Neutropenia
We are going to first focus some of our discussion there in the monitoring and management of neutropenia. Patients on CDK4/6 inhibitors should have close monitoring for the side effect. This would include a CBC with differential before starting each cycle, and because this is an early toxicity, it is recommended to have extra assessments in the first two cycles. Generally, about halfway through the cycle, we should be doing some extra monitoring, particularly with those first two cycles. Patients that are stable often do not need this beyond those first couple of cycles.
If patients have grade 1 or 2 neutropenias, this would be an ANC of 1000 or greater. We can generally just continue therapy, so no need for any dose reductions or extra monitoring at this point. For those with grade 3, this would be an ANC between 500 to less than 1000. As long as there is no fever, which is most patients are not going to be presenting with fever. We would hold the dose and then close monitoring of the counts. Once that ANC resumes to at least 1000 or greater, we can continue at the same dose level. Now if these patients have recurrent grade 3 neutropenia, this is a point where it would be helpful to consider and is recommended to consider dose reductions in that setting. Then in the rare situation where this may be accompanied by a fever or in a patient that has an ANC that is grade 4 less than 500, it is recommended to hold the dose, watch counts closely. Then once that ANC is at least 1000, resume at a dose reduction. The good news about this is while we see this commonly, this side effect is generally reversible. Holding therapy, we usually get improvement in the counts, so just something that I think is an important point as we talk through this.
[00:06:24]
Comparative Monitoring and Dose Adjustments for Neutropenia Associated With CDK4/6i
Now I am curious, Jordan, if you could maybe share some of your experience with maybe some of the challenges surrounding monitoring for neutropenia?
Jordan Hill: Of course. As you mentioned with the mid-cycle monitoring, those first couple of cycles. That can be extra either visits to see us here in Morgantown or potentially closer to home if we have patients that are travelling from far away. Typically, what we will try to do is those mid-cycle day 15 labs, whatever lab is closest to them, and then we review those in the EHR. Then the start of each cycle is typically when we are seeing them here in clinic.
That works well when they are being used in combination with aromatase inhibitors alone. It can be challenging if it is a patient who is also requiring an LHRH agonist, because sometimes the injections do not always line up with the exact beginning of the cycle depending on when those were initiated. Sometimes that does require some logistics workarounds to get to where we are seeing them on the days of their injections, but then ensuring that their lab monitoring is still occurring at the appropriate time points.
Then similarly in the metastatic setting, if you have someone on fulvestrant, the same challenges could occur. Just thinking through how to make it most convenient for patients to really ensure the monitoring is happening when it needs to occur, especially during those first couple of cycles. Like you mentioned, after those first couple of cycles, most patients are okay to just do once per cycle, so even if it does not line up exactly right, it is usually easy to maneuver around.
I will say with the agents that you discussed as having more neutropenia and ribociclib and palbociclib, we do often have to do some holds, especially in the metastatic dosing of the ribociclib, less so with the early stage dosing. Sometimes that can complicate things too, because even if you think you have their injection appointment and their clinic appointment lined up, then you end up holding and restarting their cycle at a delayed time. That can adjust the timing some too.
I will say to your earlier point about it is very reversible. They do resolve pretty quickly, and we are able to usually restart that following week. Then if it does recur or it is a higher grade and we do that dose reduction you mentioned, I do typically see that to be very effective. Usually, once we do those dose reductions, it works well for patients. Very rarely, we will change somebody to abemaciclib if we are really struggling with counts from one of the other two.
We do on very rare occasions struggle with the early stage setting where they really only qualify for ribociclib and we are struggling with those counts. It is potentially something that could be discussed about doing some off-label. Do you give them two weeks off if they are already on the lowest dose? Ribociclib is the only one they qualify for. There are some things that we could consider, but that is usually the trickiest scenario is an adjuvant patient who really only qualifies for ribociclib is already on the lowest dose still having struggles with neutropenia.
Do you continue to hold it every single cycle? Do you just say, we are just going to do a couple of weeks off? Do you discontinue the drug? Just different things that are very patient-specific. That is probably one of the more challenging, although not common scenarios that we see. Then I do to your earlier point about making sure patients know exactly what to expect earlier on is very important. If you could share what counseling points you provide to your patients to ensure that they are well educated and prepared for the recommended monitoring.
Danielle Roman: Yeah. I think really highlighting in your early patient education that the neutropenia is common and the importance of those lab draws and that close monitoring, particularly early on. I think another point that is really important is while the neutropenia is common, we do not often see infections or fevers associated with this. I think that is a reassuring point for our patients, but really also is just still making sure that they know that this is something that we need to monitor. We may need to intervene. I think setting the stage early on that the fact that it is fairly common that we may need to hold for a little while. Dose reductions might be necessary. I think emphasizing that point early on can be really helpful in ensuring our patients are going for those labs in a timely manner.
I think to your point of trying to make this as convenient as possible for patients, I think that is a really important point too. We are often trying to schedule things to help line up visits for them. It is very difficult at least from my point of view, for us to get labs on day one of the cycle, because those scripts often need to be sent in advance to a specialty pharmacy for filling.
I think sometimes the timing of those labs to make sure that we are making decisions about dose at the time we are sending the script out are really important. Sometimes we need to talk through that timing and figure out what is going to line up best for patients. I think those are some strong points on neutropenia. Certainly, the most common toxicity that we are going to talk about today.
Another one I think is a really important one to highlight is that hepatotoxicity. Sticking on the vein of lab monitoring and what we need to do for our patients. This is something we can see with abemaciclib and ribociclib. I have seen it with palbo, but it is not as strict monitoring, at least in the PI, and certainly the frequency of seeing the side effect with palbo would be a lot less. We will focus on abemaciclib and ribociclib here.
[00:12:42]
Monitoring and Managing Abemaciclib-Induced Hepatotoxicity
Jordan, I am wondering if you can share a little bit about the hepatotoxicity and what in particular we need to monitor and how we might manage this.
Jordan Hill: Yeah. Of course. With hepatotoxicity from either abemaciclib or ribociclib, they do usually recommend that mid-cycle monitoring those first couple of cycles, similar to what we discussed with monitoring for neutropenia. Then after those first couple of cycles, is where it gets a little bit different between the two agents. Thinking about abemaciclib first. After those first two cycles, where you are going to check it at midpoint of cycle, then it is monthly the next two cycles. Then as clinically indicated, after that.
I will say this can occur quite late sometimes. Even from the median onsets that we saw in the trials, it is not always within those first four cycles. We do typically continue that monthly monitoring even after those next two cycles. Per the PI, it is just as clinically indicated after those first four cycles.
Then even though it does have those close monitoring recommendations and it is a boxed warning for abemaciclib, I do typically see it a little bit less frequently than I do with ribociclib. It is still something that is very pertinent to be monitoring for and keeping an eye out for that way. As you mentioned earlier, that early identification, making sure that if we are starting to see the LFTs rise, that we can appropriately manage that.
With abemaciclib, what we usually will recommend based off of the labelling is that if they are at a grade 2, it is not needed to hold or dose reduce at that point. Those are people that I am monitoring closely. That way as soon as it hits the grade 3 and the labelling wants us to hold until it resolves to a grade 1, we can do that. Those patients that are getting to grade 2, I typically recommend a little bit closer monitoring. Per the label, as long as their bili is normal, you really do not have to hold until they get to grade 3, but at that point, you would want to hold. Then once they resolve, you would dose reduce.
[00:15:01]
Expert Recommendations on Monitoring and Managing - Induced Hepatotoxicity in Early-Stage BC
Then similarly with ribociclib, the monitoring schedule is going to look similar at the beginning, the every two weeks, first two cycles, beginning of each cycle. They recommend for the next four cycles, so a little bit longer. Again, our practice is to continue doing them monthly, just in case we do see a late onset hepatotoxicity, we are able to catch it. Then with ribociclib, they do recommend holding a lot sooner.
That is really to try to prevent those higher grade elevations. As in my experience, LFTs can get quite high from ribociclib. Additionally, they really can take a while to recover. If we can catch them earlier and hold sooner, hopefully they do not get as high, and they do not take quite as long to resolve, which maybe in the early stage setting is not as concerning. They do not currently have any disease, but can be quite problem sometimes in the metastatic setting if you are really having to hold for a long time in somebody who does have active disease.
For ribociclib you would want to hold at a grade 2 in the early stage setting. Sometimes different clinics would even recommend thinking about holding at a grade 1 just to ensure it does not get higher. You do not have to hold very long, but definitely by grade 2 you want to definitely start holding, letting it resolve and then technically resume at a lower dose.
We can have some discussion later on about what you do in your clinics. It is not a dose-dependent side effect. The labelling does recommend that you resume at a lower dose. In my experience, I do see it recur sometimes, even at that lower dose, because it is not necessarily a dose-dependent side effect. That is something that I do think is probably a little bit clinic and patient specific as well.
[00:17:12]
Danielle to ask Jordan about hepatotoxicity
Danielle Roman: Thank you, Jordan, for sharing that. I think it is good to hear that your practice mirrors a lot of what I see in my own practice. I think we do monitor, even though the PI really after those first two to four months of treatment, is a little vague in terms of the frequency of that LFT monitoring or when it is even needed, we do continue that throughout their treatment course, generally on a monthly basis.
I think it is reasonable to space it out in patients who have been very stable for long periods of time. Knowing, unlike neutropenia, this is a toxicity that can occur later. I think it makes a lot of sense from a patient safety standpoint to continue monitoring that. Then to your point about whether you would restart at a dose reduction, that has been my practice, but I can see the argument.
Knowing that this is a side effect that is not necessarily dose dependent, that we can see this recur even on lower doses. I think you could have an argument to continue, particularly in the curative setting if you are looking to maintain that. In my practice, we have more often dose reduced. With that, I think just following PI and out of concern for sometimes the degree of hepatic impairment we are seeing.
Jordan Hill: Yeah, I agree. We have actually retrospectively went back and looked at hepatotoxicity in our ribociclib patients and found that our rates of grade 3 are pretty similar to what they were in the trials, but the rates of grade 4 were still less than 10%, but much higher than what was reported in the trials which is that 1% to 3%. We do get a little bit nervous with grade 3.
Typically, with a grade 2, we are following the label we are holding, we are dose reducing, and we are resuming. With a grade 3, sometimes we will switch just out of fear that it is going to recur even at the lower dose. That could be very patient-specific, right? How high did they get? How long did it take to recover?
It might not be the same for every single person, but it is something that we do consider for some of those grade 3s. Do we want to resume at the lower dose or if they are candidate for another CDK4/6 inhibitor, do we just switch them over? As our discussion earlier, it can still happen with abemaciclib. It can be tricky in that early stage setting where we do not have palbociclib as an option.
I just anecdotally have had some patients that we did switch from ribociclib to abemaciclib in the early stage if they did qualify for both and did not see it recur. In the metastatic setting, where we know that palbociclib, even though to your point, it does still happen a lot less often, is probably the safer option. Especially if you really had some high-grade hepatotoxicity. We do at least have a little bit of flexibility, which I think is a really exciting thing for our patients, having more than one option in both settings now.
Danielle Roman: Yeah. Great points. I think another thing we always want to keep in mind, particularly in the pharmacist side of things is ruling out other causes of hepatotoxicity. We certainly know these medications can be major contributing factors to those changes in LFTs, but we also want to keep in mind other medications the patient may have started recently, supplements.
I certainly want to ask about acetaminophen. That is one notoriously if we have patients that maybe are have started that or taking higher doses could be impacting what we are seeing, alcohol intake. I think that needs to be a part of our differential as we are seeing these lab changes. We do want to have top of mind that ribociclib and abemaciclib are often contributing factors here with those LFT changes. We are going to move on to another toxicity. It Is an important one to highlight, and that is with abemaciclib-induced diarrhea.
[00:21:28]
Monitoring and Managing Abemaciclib-Induced Diarrhea
We mentioned previously that we can see diarrhea with these agents. Abemaciclib is the one that does have this unique early onset diarrhea that we do need to have close monitoring strategies. Certainly something we want to counsel patients on. We want to make sure that they have antidiarrheals on hand and that they know what to do if and when this side effect happens
For patients that are having a grade 1, so less than four stools a day over their baseline. Generally we can continue, but with the recommendations for dietary modifications, increasing oral fluid intake, and initiating antidiarrheals. Once we get to the point of being a grade 2, so this would be four to six stools over their baseline. This is something again, we want to be initiating antidiarrheals across the board, recommending those dietary changes and fluid intake.
Here we are going to have really close monitoring of our patients. We are going to watch that closely with the anti-diarrheal. If we do not get resolution within 24 hours, this is the point where we would want to hold abemaciclib and monitor for resolution to grade 1 or less. At this point, it is possible per PI to restart the medication at the same dose. However, if patients do have persistent or recurrent grade 2 diarrhea, it would be recommended to dose reduce in that setting.
For those patients with maybe higher grade diarrhea, so a grade 3 or 4, it is recommended to hold until diarrhea has resolved to a grade 1 or less and then dose reduction would be warranted with restarting here. Important monitoring point, something we should be assessing for at each visit with a patient or each touchpoint with our patients, and making sure that they have an anti-diarrheal on hand as they initiate the medication.
[00:23:26]
TRADE: Phase II Dose-Escalation Trial of Abemaciclib + HR+/HER2-EBC Planned for Adjuvant Abemaciclib
I do want to briefly talk about the TRADE information. This was a study that was presented recently. This was looking at dose escalation of abemaciclib. There has been success in other TKIs in the strategy of dose escalation to try to improve that early tolerability. This was particularly a trial of abemaciclib with endocrine therapy in those patients with hormone receptor-positive, HER2-negative early breast cancer that are receiving adjuvant abemaciclib. Patients received a 50 mg twice a day dose for the first two weeks. Then if tolerated, that was increased to 100 mg BID for the next two weeks. Then finally, up to the full dose of 150 mg PO BID.
[00:24:15]
TRADE: Primary Results
The trial here did show a statistically significant improvement in the endpoint. This was meeting that target dose of 150 mg twice a day. I think this presents us with another opportunity to help improve early tolerability for our patients. Jordan, I am curious, have you initiated the TRADE strategy in your practice?
[00:24:43]
Danielle to ask Jordan about diarrhea management with abemaciclib
Jordan Hill: We have. I am excited about the data. Similar to you, I do think it provides a nice option for our patients. I will say it sometimes is a little bit logistically challenging, at least in my experience, because a patient either has the potential to have three copays within six weeks. If you are sending it as three different scripts or a pretty high pill burden. If You are going to try to do the full titration with the lowest milligram, like the 50 mg tablets.
It does require a lot of education. From the tolerability standpoint, it does provide a very nice option to try to mitigate some of that diarrhea and allow more patients to get to full dose. I will say sometimes what we do just because of those logistical concerns is we will start at 100 mg. Still not at full dose, but then only two copays instead of three sort of thing, because unfortunately, a lot of times we will get issues with insurances covering the 50 mg tablet. I try to get it to where I can limit the copays but also improve tolerability in the best way I can.
Anecdotally, I will say that has been very beneficial. We still see improved tolerability and ability for patients to get to and stay on full dose by doing it like that, even without the full titration. Patients that were more concerned about tolerability will do the full titration. It just is a little bit dependent on the patient and how they present, what our concerns about their tolerability are, and then what financial concerns we are taking into consideration. A lot of education, of course, but it is a really nice option. What about your experience?
Danielle Roman: I would say similar experience. I love how you brought up the challenges around that dose escalation, because it is not the easiest thing to pull off in practice. Another strategy I have used on a few patients is just prolonging that escalation a little bit. The challenge at the two-week point and the scripts is real. I think there you might have a little bit of flexibility to do that 50 mg twice a day dosing for that month and then go up to the 100 BID for the next month and then to that full 150 BID. I have done that strategy as well. I like your strategy of starting at 100. It is mixing our traditional practice with the dose escalation strategy to make it all work out logistically in practice. I think that also makes a lot of sense. Anything else that you want to share in terms of your experience around maybe patient counseling with diarrhea management, anything that you are routinely instructing patients as they start the medication?
Jordan Hill: Yeah. I think this is a really important side effect to really provide a lot of education on because of how common it is. For most people, it does start early as you mentioned, and it does improve. We still have a lot of patients that really struggle with this for quite a while. I think them having appropriate expectations up front, as well as knowing exactly how to manage it, when to reach out to their care team. Obviously, as you mentioned, making sure that they have loperamide at home, are all really important aspects of early patient education.
I will say I do tend to see more diarrhea with their morning dose than the evening dose, even when they are eating something beforehand, but especially if they do not. That is another counseling point I always try to include is making sure that they are eating breakfast prior to that morning dose to try to limit that diarrhea a little bit.
Then I think loperamide is a little bit tricky for people. Everyone responds a little bit differently, and so providing that education upfront so that they know how to titrate that dose to what works best for them can really help the tolerability as well. Some people really respond well to loperamide. I have people that will only need a half a tablet, whereas some people really require a lot more. Them knowing that it is not the same for every single person and it really is very specific, can be very beneficial as well.
The other thing that I think is important to think about with diarrhea is this is one where patients will want to adjust things on their own to meet their schedule. I have some people who will just take loperamide first thing in the morning. Then they do not have to worry about experiencing any diarrhea on their way to work or needing to stop.
I have some people that it works better for them to just wait until their commute is done to take their dose. Travelling for vacations is tricky. I think just education around here are some things that you can try. The most important things is that you are not doing self-directed breaks, that you are really working with your care team to manage this diarrhea in a way that keeps you on the medication but works best for your lifestyle. I think is some other key factors that I take into consideration on initial and follow-up counseling for all of my abemaciclib patients.
[00:30:07]
Monitoring QT Prolongation With Ribociclib
Then I also wanted to just briefly bring up - we will review some data a little bit later, but I have a pretty low threshold for dose reductions for diarrhea as well, if it really is problematic for them and their lifestyle. That I think is an additional area that we can consider and we can talk more about in a little bit later on in our discussion as well.
Danielle Roman: Yeah. Great points. I think as we talk about these medications, we are talking about patients being on these therapies, taking them almost every day for two to three years, which we need to work with their lifestyles as well. I think you bring up some really great points on how to do that, how to work with our patients to ensure they are taking it, but still maintaining that good quality of life.
Jordan Hill: Exactly. One side effect that I think is also really important to touch on with these medications that are used in the early stage setting is the potential QT prolongation that we can see with ribociclib. For this particular adverse event, I do think that even though it does not happen super commonly, it is another one that really requires a lot of education upfront so that patients understand that they are going to need that EKG two weeks in to ensure that QT prolongation is not happening.
Then another really important education point with QT prolongation from ribociclib is the new medications. I know we mentioned that earlier with hepatotoxicity, but I think it is really important here too, to make sure that patients are aware if they are considering starting any new medications to let the care team know.
That way, we can ensure that it is safe to do so. Then specifically in regards to their treatment for their breast cancer, another caveat with this is it is contraindicated with tamoxifen. If we do have somebody that is really struggling to tolerate aromatase inhibitors, that does limit our flexibility a little bit in their endocrine therapy partner because of this potential QT prolongation that we can see.
[00:32:26]
Jordan to ask Danielle
I am curious for you, Danielle, the added level of complexity sometimes is with the right QTc. I am curious at your center if the QTcF is reported in the EHR, if that is something that you are having to calculate and what that experience has been like for you.
Danielle Roman: We do not get a QTcF as part of our EKG report that is coming through. It is something that we do need to calculate outside of our EMR. I have found that there are a number of online calculators that are very helpful. You do need to have some additional information about the patient. You do need to have their heart rate and be able to input that as well as some information from the EKG, into the calculation to get the QTcF. I am guessing there is other institutions that are having to do the same thing. I think it is just a really important point that it is not necessarily the same, and we need to confirm that we are actually calculating or looking at a QTcF as we make any recommendations per the PI. How about you, Jordan?
Jordan Hill: Ours is a little bit unique in that our EKG machines do have the QTcF, but it does not pop up in our EHR. We either have to go to a different software to find it, or we have to use an online calculator similar to you. I do a little bit of both, but it is definitely an extra layer of complexity that we have to take into consideration.
[00:34:03]
Key Talking Points
Danielle Roman: We had just had a lot of discussion on adverse effects, some really important ones. I think a lot that drives back to early principles of patient education and our monitoring strategies so that we can hopefully keep patients on these therapies that we know are very efficacious in that high-risk early stage setting. We have talked through some of these already, but I do want to have some additional discussion about adherence strategies and how we can work together as a healthcare team to keep patients on treatment. We mentioned that there is a lot of complexity happening for these patients. There is oftentimes with these high risk patients, they have had chemotherapy, surgery, radiation.
They are receiving endocrine therapy, and now we are adding on this targeted agent that we are talking about a long duration of depending on a drug. If it is abemaciclib, generally two years. Ribociclib, we are talking three years of treatment. There is a lot of complexity here. I think one area that requires some discussion is the financial toxicity for our patients. Jordan, I wonder if you might be able to comment on your experience here and anything that your team is doing to help monitor for this?
Jordan Hill: Usually up front, prior to the scripts going out, we usually counsel patients in clinic the day we are planning to send the script and so I am able to educate the patient. These sometimes can be very expensive. If the pharmacy does call with an unaffordable copay, please let us know. We are fortunate that we do have a health system specialty pharmacy, and so we have a lot of communication back and forth with our specialty pharmacy, which I think is very advantageous.
Even without that, I think the patient understanding when to reach out to let us know so that we can potentially find other ways to make this medication affordable, whether that be copay cards or patient assistance programs. These medications all have grants, lots of options available. Ensuring that the patients know that they may qualify for assistance, but we cannot assist with that process if we do not know.
Then lots of different care team members are going to be involved, whether that be a social worker, members of the specialty pharmacy team. I think the most important part is ensuring that the patient knows there is the potential for that high cost to be there. There are options that can make it more affordable so that we do not run into the scenario of them just refusing the medication and no one knowing until the next time they come to clinic, is the primary avenue that I approach the financial toxicity component.
Danielle Roman: I have a similar practice as well. That education up front, very important. Frequent touch points with our patients, I think are all is also really important. That is even patients that have been on this for the long term. We may have opportunities to space out those touch points for patients that are having great tolerance. I think still maintaining some regular cadence with a touch point so that you can even talk about things like any anticipated financial toxicity, how to adjust for changes in vacation schedules and things like that.
I think all of that is really important. Having ideally a team approach to financial toxicity. Working with specialty pharmacies. We have a dedicated group of nurses that helps with this process along with our pharmacy colleagues. I think another challenging time point is that the point where we are getting to the first of the year where patients may have new insurance plans or the deductibles resetting.
That is often a time point that we need to make sure that patients have a plan in place for any changes in that financial burden. I do also want to touch on some of the key talking points because we have talked through toxicities and the need for frequent dose holds and dose reductions. Sometimes that can be a really scary thing for our patients. It can also be something, as a healthcare provider, that we try to avoid with those dose reductions out of concern for impacting the efficacy and particularly efficacy, maybe in the early stage setting where we are talking about curing the patient.
[00:38:45]
Maintaining Adjuvant CDK4/6i Therapy to Maximize - Risk Reduction
One of those points I want to bring up is just the fact that we do have some data from both the NATALEE and monarchE trial showing that adjusting the dose is success and not failure. Following those protocol-guided interruptions and dose reductions to maintain the benefit also helps to keep patients on treatment and is not impacting the efficacy of the medication.
[00:39:13]
monarchE: Abemaciclib Benefit Is Maintained With Dose Modifications
We have some reassuring data from these trials showing that the benefit of both of these agents is maintained even in the face of dose reductions.
[00:39:24]
NATALEE: IDFS by Dose Reduction
In four year invasive disease-free survival with abemaciclib. Also data coming out of NATALEE trial showing that invasive disease-free survival is maintained at landmark analysis. I think is a really important point to share with providers that may have some hesitancy as well as our patients that may be hesitant to proceed with a dose reduction in this setting. Jordan, I am curious if you have had the opportunity to share this information in your clinical practice with your patients?
[00:39:56]
Danielle to ask Jordan about patient education
Jordan Hill: Absolutely. I 100% agree. I think it is not just scary for the healthcare team. It is also scary for a patient to have to have a dose reduction. This data has been extremely helpful in that conversation. I try to incorporate it in my initial education because the last thing I want is for them to stop the medication altogether, especially without us even knowing, which can happen if they are feeling really poorly and we are not knowing.
In addition to all the things that we have already talked about as far as educating them and early monitoring and management, I think one of the important things for them to understand is that we do have the option to go down on the dose, and the outcomes are exactly the same. If you are not tolerating it, we will try a dose reduction. A lot of times, patients tolerate it much better. Them knowing upfront that there are potentials to make that dose more tolerable for them can really help with adherence and the anxiety, to your point.
Danielle Roman: Yeah. It is very anxiety-provoking. I think as we talk about patients just wanting to like suck it up and push through. I think again, talking long-term, that we need to get these patients through two to three years of therapy. There are strategies we can do to improve their quality of life and to get them through those years. I think setting the stage upfront with some of this information can be really important so that they do not feel like there is any failures in reporting this back to us. In fact, it actually is helpful for us to have this information and hopefully keep them on treatment longer.
[00:41:45]
Optimizing Education and Communication
I am curious, Jordan, if you could share just overall, any strategies you found are beneficial in patient education, like who is educating your patients? What information is being provided? Is it verbal, written? Is there anything that you found to be helpful setting the stage as patients start these medications?
Jordan Hill: Absolutely. As I mentioned, we try to counsel everybody in person in clinic the day the script is being sent. I do find that that provides a lot of value. It is not always possible. Sometimes that education is going to have to be virtual. There is always things that come up that may not make it possible, but I do think that in-person education really does provide a lot of benefit to our patients. Not just in the level of understanding, but also the level of comfort with the new medication but also with you, and the sharing of potential side effects that may come up later on.
Then we also have the benefit of having that health systems specialty pharmacy. Even though we provide comprehensive education in person, they do get some reiteration of that education before the script is being dispensed from the pharmacists at the specialty pharmacy as well. A lot of times our patients are able to receive that initial education in person, receive written information from us.
We typically here at our center use the education sheets that are developed by HOPA, ONS, and NCODA. Then they have a chance to read and digest, and then get that second education from the pharmacist at the specialty pharmacy. We found that that really can be quite beneficial for the patients, not only comfort level, but retaining of the information and knowing what to expect as well.
Danielle Roman: I would say similar experience in our end. We prefer in-person visits whenever possible, but do make virtual options available for our patients. I think it is really helpful to have a multi-disciplinary approach to education. Patients will often meet with the pharmacist, a nurse, and then sometimes the advanced practice provider is included in those visits. Another strategy that has been really helpful in our practice is providing patients with a calendar.
As we think about ribociclib and palbociclib in particular, they need to track weeks on and weeks off. For abemaciclib, it is twice-daily dosing. I think for certain patients use of a calendar and even check boxes next to the dose for the day can be really helpful to track that information and make sure we are all on the same page.
[00:44:28]
Measures to Increase Oral Oncology Treatment Adherence
Jordan, any particular strategies you are using for adherence, outside of calendars, anything else that you are routinely doing for these agents or recommending for patients?
Jordan Hill: I think routines are super important as well. I think calendars are very beneficial. Then in addition to that, if you can tie in their timing of the day that they are taking their medication with something that is in their regular routine, it is a lot easier for them to remember.
[00:44:56]
Strategies to Address Potential Barriers to Care
Then always providing them with some additional strategies anytime they are outside of their normal routine, like going on vacation, and things like that.
Danielle Roman: I think for some people, cell phone alarms are really helpful. You just really have to find something that works for the patient. Really just making sure that they know that we are a support system with them through all of this. Making sure that they know how to contact their team when they need to report that side effect, when they are having issues with financial toxicity, that they have just an important point of outreach with a particular person that they know they can get on the phone or see in clinic, and that they build that relationship with the team.
I think that that is invaluable, that as they start these therapies that they feel supported by the healthcare team and whoever is that point of contact, whether it be a pharmacist, a nurse a technician at specialty pharmacy, a provider. I think just making sure that they know they have that support system and we are able to provide that for them is really important.
[00:46:00]
Oncology Pharmacy Think Tank: Patient-Centered Management of CDK4/6 Inhibitor Therapy for HR+/HER2-Breast Cancer
Thank you so much, Jordan. We have covered a lot today. Hopefully, everyone is feeling a little bit more confident about what we are monitoring for and how we might manage these side effects, and really how we just holistically manage these patients as we help to get them through these long courses of treatment. I really appreciate your insights, Jordan, and nice talking with you.
Jordan Hill: Thank you.
Danielle Roman: To claim CME credit for this activity, please click on the claim credit button on your screen.
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