InterACT Oncology Team Training: Equipping the Interprofessional Team With Personalized, Patient-Centric Therapeutic Strategies for Patients With High-Risk HR+/HER2- Early Breast Cancer

So the first trial we want to discuss is monarchE.

So this was the adjuvant trial that looked at the adjuvant use of the CDK4/6 inhibitor abemaciclib. And let us take a moment just to review the trial population. And this, of course, helps define who would be eligible for this agent.

So this trial looked at patients with high-risk node-positive HR+/HER2- early breast cancer. It did not matter if they got prior chemotherapy or not. They had to be 16 months or less from surgery to the time of randomization and 12 weeks or less of endocrine therapy.

And the population had 2 different cohorts, and together the cohorts were looked at for the intention-to-treat population. So the first cohort, which was the vast majority of patients, 91%. These patients had 4 or more positive lymph nodes or 1-3 positive lymph nodes plus an additional high-risk feature, either grade 3 disease or a tumor 5 cm or larger, so T3.

Cohort 2, much smaller, this was a group that had 1 to 3 positive lymph nodes, but specifically had a Ki-67 20% or higher and then did not have an additional high-risk feature, so either not grade 3 and not T3, so grade 1/2 or tumor size less than 5 cm in size. And patients were randomized to standard endocrine therapy versus standard endocrine therapy plus abemaciclib 150 mg twice a day for up to 2 years. And the primary endpoint was invasive disease-free survival.

Next slide.

[00:08:42]

monarchE: iDFS

And so this is pretty hot off the press. We saw an update on this trial at the recent ESMO conference and really impressive as we get further out.

So now, with the median follow-up of 76 months, we see that the benefit persists, and actually these curves widen. So at this most recent report, the hazard ratio was 0.734, so highly statistically significant. The invasive disease-free survival rate for the group with abemaciclib was 77.4% versus 70.9% for the group without abemaciclib.

Next slide.

[00:09:18]

monarchE: OS in ITT (Key Secondary Endpoint)

And so overall survival was a key secondary endpoint, and at ESMO they were able to report this, and it actually did reach statistical significance, which is hard to show in this setting. So it did show a hazard ratio of 0.84, and that did reach significance.

Next slide.

[00:09:42]

NATALEE: Adjuvant Ribociclib + ET in Intermediate- to High-Risk HR+/HER2- EBC

So now let us switch gears a bit and think about another CDK4/6 inhibitor also approved in the adjuvant setting, ribociclib. So the big difference here is that while this trial included patients with high-risk disease, it also included patients with what is defined as intermediate-risk disease. So we will take a moment to review the eligibility population here.

So these were patients that could have stage IIA disease, so either node-negative disease that had to be either grade 2 with a high Ki-67, 20% or above, or high-risk via genomic risk profiling, or could be node-negative with grade 3 disease, or could simply be N1. And then otherwise, anyone with lymph node involvement could be enrolled as well.

And the randomization was to ribociclib plus endocrine therapy versus standard endocrine therapy, and notably the ribociclib dosing is 400 mg. So this is lower than the metastatic dosing of 600 mg, and this drug is dosed 3 weeks on, 1 week off, and they used it for 3 years. And again, the primary endpoint was invasive disease-free survival.

Next slide.

[00:10:56]

NATALEE: iDFS

And so this is the most recent report, again from ESMO, now with longer follow-up, looking at the invasive disease-free survival. So we see a delta between the 2 groups with a median follow-up of 55.4 months. The delta is 4.5%. So we see it is growing with time; has a ratio of 0.72. The overall survival data was not yet mature.

Next slide.

[00:11:21]

NATALEE: iDFS in Node-Negative Subgroup

And so importantly, of course, unlike monarchE, the NATALEE trial included a group of patients with node-negative disease.

And so it is of high interest to understand are our CDK4/6 inhibitors helpful in this group as well? And it showed it was. So again, with longer follow-up, we now see a delta between the 2 groups of 5.7%. Again, showing a benefit even in the intermediate-risk population.

Next slide.

[00:11:51]

Approvals and Recommendations: Adjuvant Abemaciclib + ET

And so what is a summary of the approvals that we have? So for adjuvant abemaciclib, here we have a list of how it is described by the FDA, ASCO, and CCN.

So the FDA, the initial approval was a bit more detailed and stricter, calling for the Ki-67 to be 20% or higher. That requirement was dropped in March 2023, and now it is a pretty broad label. It simply says node-positive HR+/HER2- early breast cancer at high risk of recurrence. While ASCO and NCCN really more describe the patient population of the trials.

Next slide.

[00:12:32]

Approvals and Recommendations: Adjuvant Ribociclib + ET

And so for ribociclib, the summary, again, is here.

The FDA says stage II/III, HR+/HER2-, early breast cancer at high risk of recurrence. And again, ASCO and NCCN tends to be more specific, describing the study populations.

Next slide.

[00:12:50]

monarchE and NATALEE Trial Populations

This is a slide I find very helpful. I am in my clinic right now, and I tend to have this hanging up. And it is a really good reminder to help compare the study populations in the 2 trials.

So this is just a nice way to look at it side by side to see who would meet eligibility for which drug or for both drugs. And as you see, there are a couple of interesting items here. So, for example, lymph node micrometastases actually were not allowed in NATALEE, but they were in monarchE if there was also a high-risk feature, grade 3 or Ki-6767, 20% or above. Of course, when you have options, you want to share that with patients, review it, and the treatment choice can depend on a number of factors, right, access, risk, long-term efficacy, the safety profile. As we will get into, these drugs have different side effect profiles as well.

So maybe I will pause for a moment and ask Susan, from a patient perspective, when it might be a situation where there are 2 drugs that one is eligible for, how would you prefer to hear that information from an oncologist?

Susan Ogden: So, I mean, one of the things that occurs to me when I am looking at these charts, when you are looking at percentages, it does not mean a whole lot to a layperson. It would mean a whole lot to me if you were saying, like, this means in 100 more women it will not recur if they take this. And so a chart like this would not mean anything to me if I saw it in a clinic.

I would need it to be put into very lay and very personal terms.

Dr Spring: And then in terms of comparing 2 drugs, of course, side effects would be of interest, but also, the efficacy data in thinking, as we reviewed the trials, clearly the design is different, you know, 2 versus 3 years is different. So in terms of helpful advice for how to share.

Susan Ogden: So if I am going to have side effects, I would want it to be more effective. So that would be one factor. And I also want to say that it is going to vary quite a bit on the age of the patient, but I am sure you already know that.

Dr Spring: Yes, I think we will actually have some specific slides on that one as well. That is very important. Yes, I think that is a great point in terms of describing it in more specific numbers out of 100 patients.

And I also tend to say as well, like what actually gets considered clinically meaningful in oncology, right? So 5% means a whole lot to us in oncology. That is not always an impressive number, though, to everyone.

But then we also think if you are reducing recurrence risk by, say, 5%, for that 5%, those 5 patients, that recurrence is a really big deal. That is obviously a life-altering situation. So that is different than how we might think of 5%, of course, in other settings.

Susan Ogden: And even if you are using these sort of stick figures to show that there are 10 people, 10 stick figures, and one with this drug, only one will have a recurrence type of thing.

Dr Spring: Great point. Well, thank you.

Let us move on to the next slide.

[00:16:22]

NATALEE and monarchE: Tolerability and QoL

So again, kind of along the lines that we are speaking of a bit, this is some data comparing tolerability and quality of life between the 2 agents and looking at the grade 3 or higher adverse events.

So these drugs, which we will get into more, do a very different safety profile. So diarrhea is a more common AE with abemaciclib, while with ribociclib, we see more issues with the labs, more neutropenia, more liver toxicity. Both can have some fatigue.

So overall in the studies, due to side effects, 18.5% of patients discontinued abemaciclib, while 20% of patients discontinued ribociclib.

Next slide.

[00:17:06]

Dosing and Schedule Considerations for Adjuvant CDK4/6 Inhibitors

So some other considerations as we compare and think about these 2 agents.

So as we reviewed before, the schedule is different, right? Abemaciclib is dosed twice a day and continuously, while ribociclib is once a day, but it is 3 weeks on, 1 week off. 400 mg of a pill comes in 200 mg, that involve taking 2 pills.

The timing for starting a CDK4/6 inhibitor did vary between the 2 studies. So for abemaciclib, it had to be started sooner after endocrine therapy, while for ribociclib, you could already be on endocrine therapy for almost up to a year. The duration, of course, is different. Two years for abemaciclib, ribociclib, 3 years.

And in terms of the choice of endocrine therapy, for ribociclib, they focus on the aromatase inhibitors. So of course, if you have a woman who is premenopausal, that would mean using a GnRH agonist as well. For abemaciclib, they did allow tamoxifen, but of course, it is known that both abemaciclib and tamoxifen do have a small VTE risk. So in practice, many try to avoid that combination if they can.

And then in terms of drug-drug interactions, both drugs do have some drug-drug interactions. So certainly, I think you have situations where you are speaking with a patient and they might have an obvious contraindication to one of the agents. So it is important to look at the other medical history as well as the medication list as well. And then there are recommendations for patients who are 75 years or older to consider starting abemaciclib at 100 mg twice a day and then could escalate to the full dose of 150 mg if tolerated.

Next slide.

[00:18:51]

Insights on Treatment Selection From a Focus Group of Patients With High-Risk HR+/HER2- EBC

And so let us think a bit about insights on treatment selection from a focus group of patients. So this was a focus group of 9 patients with different histories. They all had some different situations. But some of the key insights that were learned was that overall, mixed experiences in terms of how treatment options were explained to them. And overall, there was a desire and a need for comprehensive discussions of all treatment options and potential side effects.

Some noted issues with the genetic testing process and just post-diagnosis communication in general. And overall, it was emphasized the importance of respecting patient preferences and involving them in treatment decisions.

Susan, anything to add on this focus group?

Susan Ogden: So I think one of the most important things that was said to me after surgery was that I was cancer-free. You do not have cancer right now, and we are going to recommend some different treatments so that you do not get cancer again. Because the risk of recurrence was not something that I even considered until I was past surgery.

So I think staging the information that you share with patients is very important. There is so much emotion and so much fear at the beginning, we cannot absorb it all. So tell me I am cancer-free, and I really want to make sure that you stay cancer-free. Then introduce the various options.

Dr Spring: That is a great point, even just thinking of my experiences in clinic today. I saw some patients who are a bit further out from their initial treatment, and some asked me some questions that certainly we reviewed back at those early appointments, but as time passes and they have a chance to absorb more, it is a good reminder that it is important to do those overviews at the time and help summarize as well.

Great. Next slide.

[00:20:48]

Treatment Algorithm for Adjuvant Therapy in HR+/HER2- EBC

So here is a proposed treatment algorithm for adjuvant therapy in HR+/HER2- early breast cancer, separated out by number of lymph nodes involved.

So for N1, or 1-3 positive lymph nodes, based on available data for women who are premenopausal, adjuvant chemotherapy is generally considered, although there is a current trial offset that is looking at this issue and perhaps focusing on ovarian function suppression endocrine therapy instead may be equivalent, so that is an opportunity there. Versus for postmenopausal women with 1-3 positive lymph nodes, we do rely heavily on genomic testing, and if it is low-risk, favor adjuvant endocrine therapy alone. High-risk chemotherapy followed by endocrine therapy.

And then in terms of eligibility for CDK4/6 inhibitors, that is where some of the other factors play a role with 1-3 positive nodes. So if the tumor is grade 3 or the tumor size is 5 cm or larger, one would be eligible for either abemaciclib or ribociclib. With 1-3 positive lymph nodes without an additional high-risk feature, they would still be eligible for ribociclib.

And, of course, I just want to remind everyone, obviously, the importance of genetic testing and that patients may, with a BRCA mutation, be eligible for olaparib in certain scenarios as well. For 4 or more positive lymph nodes, this group does fit under the criteria for abemaciclib. The caveat could be if someone also had a BRCA mutation, we would typically consider olaparib.

Next slide.

[00:22:30]

Let's Revisit a Question

So let us go back to one of our questions.

[00:22:34]

Patient Case: Woman With Grade 3 ILC and 2 Positive Nodes

So this is our case.

Recall a woman with invasive lobular carcinoma. So she presented with a mass, positive lymph node ER 80%, PR 30%, HER2-, genetic testing negative. Had upfront surgery. The pathology revealed a 4-cm invasive lobular carcinoma. Two of 3 nodes were positive, so, staged as T2N1. Oncotype score 26. Received TC times 4 cycles, followed by adjuvant radiation. She returns now to discuss treatment options.

Next slide.

[00:23:10]

Posttest 2: In addition to extended-duration adjuvant endocrine therapy, what additional systemic therapy would be an appropriate treatment for this patient?

So in addition to extended-duration adjuvant endocrine therapy, what additional systemic therapy would be appropriate? And 5 answer choices for you there.

All right. We have now about 30% saying endocrine only, 10% saying ribociclib only, and then 30% abema or ribo, and 30% for abema, palbo, or ribo. So we did not review the PALLAS study looking at palbociclib, but that ended up being a negative study. So palbociclib is not approved in the adjuvant setting.

Next slide.

[00:24:10]

So the correct answer is D, abemaciclib or ribociclib. The rationale here is that this patient is considered at high risk of recurrence given the presence of 1-3 positive nodes, grade 3 disease, and high-risk oncotype. So she is eligible to receive either abemaciclib or ribociclib based on the monarchE and NATALEE trials.

All right. Next slide.

[00:24:34]

InterACT Case Simulation and Discussion

Please send your comments

So at this point, people could send in any comments, and we will have a chance to discuss them as well.

Next slide.

[00:24:46]

Returning to the Patient Case: Woman With Grade 3 ILC and 2 Positive Nodes

So this is just reminding us of our case again, and we can go to the next slide.

[00:24:54]

Poll 2: Which of the following topics related to treatment would you like the faculty speaker and patient advocate to discuss?

Okay. So based on that recent case, we want to poll people to see which of the following topics related to treatment would you like us to discuss next? So we have several options for you, and we will use how you vote to tailor our conversation.

Can we open polling?

All right. So I think all the topics are of interest, but we got the most votes for helping patients with financial and logistical challenges. So maybe open it up to Susan to maybe give her initial thoughts on that challenging topic.

Susan Ogden: I do not know how much to say about financial challenges because I did not have any. I fortunately was on Medicare, had already been eligible for Medicare, and Medicare paid for my entire treatment. So it is such a sad topic in the United States, honestly, to have to be concerned about that. I would really need to ask somebody with more expertise on helping people with the financial side. I assume the drug companies have some kinds of programs for helping patients.

Dr Spring: Yes. That is what I was going to add. So I think here we are fortunate to have a lot of different resources that kind of help us in the clinic, including financial counselors who are available and also more like resource specialists who are in touch with all of the companies of the agents we commonly use and are very aware of their financial assistance programs.

So I think a couple of things that sometimes come up are there may be some paperwork or something we need the patient to sign or help with in order for maybe them to get that co-pay assistance, for example. So it sounds small, but I always warn people, like, answer all phone calls because you may be getting a call from the company or just from a pharmacy or someone that is trying to help, but they need to get through. But I think that having that team available, and I do think that companies really do want to help. And I think our resource specialist knows the representative from each of them and is able to get patients as much help as they can.

It can come up occasionally too, obviously, if a patient's eligible for a couple of different options with different insurances, there sometimes is one that is more affordable. So that is, of course, something to try to explore as well. I think logistical challenges, that is obviously a broad topic too.

I do think the packaging, for example, the CDK4/6 inhibitor tries to help in terms of remembering how to dose them, for example, with a ribociclib 3 weeks on, 1 week off. I think the packaging does really try to be helpful there, but can think about even day of the week that you start. For some people it is really much easier for them, for example, starting on a Monday. But if Thursday is one of my big clinic days, so a lot of patients I have on these agents may start on a Thursday, kind of get their labs done, and then start. So sometimes some of the small things can go a long way.

Let us see, we had a tie in terms of the other topics. So maybe I will let you pick, Susan, if you look at some of the other topics, any more advice you would have related to any of them.

Susan Ogden: So in terms of side effects, it seems like what is helpful to me is if the doctor talks to me about some patients have these side effects, not everybody has it. So as you are listening to this, you could put yourself into the "some" but maybe not "me" category, which makes me more open to hearing it. And the side effects can be managed too.

Some patients have had success managing them. So again, giving the patient the idea that you do not have to be the patient that is really laid low by these. Some patients have it and are able to manage it. So I think that can be an effective communication tool.

Dr Spring: That is a great point. I think it is overwhelming too, whether you get a handout in clinic or from the pharmacy and you see that laundry list of side effects. You definitely need some context around that, or else I do not think anyone would be excited about taking anything because every possible side effect has to be listed there.

I know we have spent some time talking about how we present data. We will have some more opportunity to discuss as well, but why do we not move to the next slide?

[00:30:16]

Strategies for Managing AEs and Promoting Adherence to Adjuvant CDK4/6 Inhibitors in EBC

So now we are going to shift gears and talk about strategies for managing AEs and promoting adherence to adjuvant CDK4/6 inhibitors.

[00:30:27]

Patient Case Continued: Woman on Adjuvant Abemaciclib With Diarrhea

So the same case, but we are going to kind of move on to the next part of it. So this was the woman, 58-year-old, postmenopausal, T2N1, high-grade invasive globular breast cancer, HR+/HER2-.

She ended up starting adjuvant ibuprofen 2 months ago. She calls to report side effects, including 6-8 episodes a day of diarrhea despite taking as-needed antidiarrheal medication. And then she says her weight is stable. She is eating and drinking without problems. She also notes fatigue despite adequate sleep and is having trouble returning to work as a result.

You ask her to hold abemaciclib until her symptoms are resolving.

Next slide.

[00:31:10]

Pretest 3: What additional counseling would you provide for this patient as the most appropriate next step in her treatment?

So pretest question 3. What additional counseling would you provide for this patient as the most appropriate next step in her treatment? Four options for you there. We will let everyone review, and then we can open polling.

All right, so the vast majority said she should restart abemaciclib with a dose reduction and continue antidiarrheals as needed.

Next slide.

[00:32:00]

Key AEs With Adjuvant CDK4/6 Inhibitors: Monitoring and Prevention

So here is a summary of the key adverse events with the adjuvant CDK4/6 inhibitors.

So diarrhea could be seen in both, but much more common with abemaciclib. Importantly, to educate on antidiarrheal therapy, typically over-the-counter, but want to make sure that is available to patients at home. It is important to increase oral hydration and to notify the team if it is an issue.

And I think it is important also to educate on quantifying, because that is how we grade diarrhea. So we might have to educate the patients and say, you know, we actually will ask you, like, how many episodes in a day. Does that help to inform us if we need to hold or not? And dietary modifications can be quite helpful as well. You know, we have had patients sometimes meet with nutrition, and they found that quite helpful.

In terms of hepatobiliary toxicity, that, again, can be seen with both agents, but we see it more with ribociclib. And then neutropenia, again, can be seen with both agents, but we see it more with ribociclib. And in terms of, you know, how we follow these AEs, it is really our labs. So for the first couple of months on these agents, we are checking labs every 2 weeks and then monthly after that, or as clinically indicated.

VTE is rare, but does happen to increase rates with abemaciclib, so, important to educate on that. As I commented before, we do often try to avoid using abemaciclib with tamoxifen for that reason.

In terms of ILD and pneumonitis, they can, of course, happen with any agent, so there is a small risk of that happening with both abemaciclib and ribociclib, so, important to monitor for pulmonary symptoms such as hypoxia, cough, shortness of breath.

QT interval prolongation is something that is seen with ribociclib. The 400 mg dose, the incidence is actually quite low, and so the recommendation is to get an EKG at baseline, and then again 2 weeks after starting ribociclib. And then beyond that, you typically do not need to check again unless perhaps they are on a new medication that may also influence the QTc. Then, of course, we will also be just keeping an eye on the electrolytes as well with the lab checks.

Next slide.

[00:34:22]

Management of Abemaciclib-Induced Diarrhea

So here is a helpful algorithm to summarize how to manage abemaciclib-induced diarrhea.

So these are the types of tools that can be helpful. If there is a triage RN office at the clinic, this is the type of algorithm that could be helpful to have handy. So importantly, is to initiate antidiarrheals at the first sign of loose stools and encourage increased oral fluid intake.

Then from there, it really depends, as I said, on the grade of the diarrhea, and that is where the number of episodes matters. So grade 1 is defined as less than 4 stools a day over baseline. With that happening, abemaciclib can typically continue without a dose modification.

Grade 2 is 4-6 stools a day above baseline. From there, it depends on how long it takes to resolve to grade 1 or better, and if it takes longer, that is where we would reduce the dose. Grade 3 is 7 stools a day or more above baseline. There we would hold until it resolves to grade 1 or better and then reduce the dose. Same thing with grade 4. That would be considered life-threatening consequences or urgent intervention indicated. So the dose reduction would be from 150 mg to 100 mg, and then the final dose reduction is 50 mg. As I mentioned before, dietary modification would be helpful, so low fiber, low fat, smaller, frequent meals.

Next slide.

[00:35:50]

Monitoring and Management of Ribociclib-Induced Hepatotoxicity in Early-Stage Breast Cancer

In terms of hepatotoxicity, it is a monolith in early breast cancer. As I mentioned, it is important to check the labs more frequently early on, so every 2 weeks for the first 2 months. From there, in terms of how you handle it, it depends, again, on the grading, which is relative to the upper limit of normal for your institution.

So if it is up to 3x the upper limit of normal, that is grade 1, and you do not need to adjust the dose. And then for grade 2, which would be 3-5 times the upper limit of normal, it does have to be held. You can resume at the same dose level, but if it recurs, you would hold and reduce the dose.

For grade 3, you are always reducing the dose if you do start again. But I think these expert recommendations here are helpful because, really, this is not so much a dose-dependent issue. So it is not that we are seeing much less of it with 400 mg compared to 600 mg, for example, in the metastatic setting.

And so, you know, I think a lot of times if you have a significant issue with the LFTs, if it is more significant, I think the majority of us do not actually try the lower dose. That is where we may, for example, discuss abemaciclib if that is an option. But for more mild elevations, I think sometimes there certainly a dose reduction could be helpful.

So we will go to the next slide.

[00:37:16]

monarchE: Dose Modifications and Discontinuations due to AEs

So this is just some data from monarchE looking at dose modifications and discontinuations due to AEs.

Not surprisingly, the most common reason for dose hold was diarrhea, and then that was followed by low white blood cell count and then followed by fatigue. And then, same thing with dose reductions. Diarrhea was the most common reason. In terms of full discontinuation, that rate, as I said before, was 18.5%, and the most common reason, again, was diarrhea.

Next slide.

[00:37:52]

monarchE: Dose Modifications and Discontinuations due to AEs by Age

And so this is interesting. This is breaking it down by age.

So it did seem, not surprisingly, patients 65 or older did have more frequent abemaciclib dose adjustments. And certainly if 75 or older, as shown here, seeing it broken down by age 65 versus above, the number of discontinuations was 15% versus 38%.

Next slide.

[00:38:21]

monarchE: Predictors for Abemaciclib Discontinuation

So this was a study looking at the predictors for abemaciclib discontinuation from the monarchE study, and overall the conclusion was that in terms of patient population that needs more closer attention and counseling would be older patients. So not surprisingly, those who are postmenopausal, any patient with comorbidities, and actually patients with less lymph node involvement. Not surprisingly, those at higher risk were more apt to actually continue on the medication.

Next slide.

[00:38:59]

monarchE: Dose Reductions and Efficacy of Adjuvant Abemaciclib

But I think this is very helpful to see, and this is actually data I share with patients quite often, and this is that if you do need to reduce the dose, dose reductions were not associated with decreased benefit.

Susan, if I can ask you from a patient perspective, is this type of information helpful to hear early on or more helpful to hear if a provider is discussing a dose reduction?

Susan Ogden: I think if you are discussing a dose reduction, this would be a good time to share that, because if the patient is motivated to be on the drug, they want to maximize the benefit. And so if you are talking about reducing it, there is this fear that it will not work, and what am I going through all of these adverse effects for? So I think when they are beginning to have the adverse effects and you want to reduce the dose, reassuring them that it is still going to be highly effective would be a really important thing to share.

Dr Spring: Yes, and this has been seen across all 3 CDK4/6 inhibitors. Of course, it comes up in the metastatic setting as well. And this is not always the case, of course, for all our agents. For example, the PI3 kinase inhibitor, those reductions there in the advanced setting are not like this. You know, we do see decreased efficacy with the lower doses.

So I agree. I think this is very important and helpful to share.

Next slide.

[00:40:23]

TRADE: Phase II Dose-Escalation Trial of Abemaciclib + ET in HR+/HER2- EBC Planned for Adjuvant Abemaciclib

So this is an interesting study called the TRADE study that looked at dose escalation of abemaciclib in the appropriate patient population.

So this was similar to a study in the HER2+ setting that looked at the drug neratinib starting at a low dose. That is another agent that is associated with a lot of diarrhea. In that study, they, again, started low and went up.

So this is essentially doing the same thing with abemaciclib. So for the first 2 weeks, started at the lowest dose at 50 mg twice a day. Then the second 2 weeks at 100 mg twice a day. And then after that first month, the goal was to be in the full dose of 150 mg twice a day.

[00:41:08]

TRADE: Primary Endpoint (Composite Adverse Event Rate at 12 Wk)

If we look at the next slide, we can see that. So 70.8% of patients in the trial did reach target dose, which is higher than what was seen in monarchE, where 60% of patients were on the target dose. So I think this is certainly a helpful strategy for anyone who is particularly concerned about AEs or maybe has some comorbidities or is older. I usually give this as an option. I think some patients do prefer just to start at the full dose and decrease if they have to, while others, this makes them much more comfortable to start low and increase from there.

Susan, any comments on this approach from a patient perspective in terms of starting at the standard dose and potentially having a drop versus starting low and moving up?

Susan Ogden: So this is really such an individual choice. I mean, I am a competitive person, so I would want to start on the highest dose and see if I could maintain that. Other people might be more cautious.

Dr Spring: Yes, I think that is a key point, right? This is really about shared decision-making and really, I think this is where I think patient about preferences. I think, either approach is perfectly fine, so, important to share that. So thank you.

Next slide.

[00:42:32]

Let's Revisit a Question

So let us revisit our question from before.

Next slide.

[00:42:36]

Patient Case Continued: Woman on Adjuvant Abemaciclib With Diarrhea

So this, as you recall, this woman had started her abemaciclib. So 2 months ago, called to report the 6-8 episodes a day of diarrhea despite taking appropriate antidiarrheals, weight was stable, eating and drinking okay, was having fatigue as well that was impacting her ability to return to work. So, she held the abemaciclib until symptoms are resolving.

Then, next slide.

[00:43:00]

Posttest 3: What additional counseling would you provide for this patient as the most appropriate next step in her treatment?

So what would you advise her? Four options for you to choose from there, in terms of how you would advise her on the most appropriate next step in her treatment.

So we will just give people a moment to read, and then we can open the polling.

Okay, great. So the majority chose B, she should restart abemaciclib with a dose reduction and continue antidiarrheals as needed, which is the correct answer.

Next slide, or we can show the answer.

[00:43:55]

Yes, so the rationale here is that this would be considered grade 3 diarrhea, so certainly holding is appropriate, but then when you resume, you should use a dose reduction. And then if a dose reduction strategy does not work, of course, there is a situation where she is eligible for either agent, and so switching to ribociclib could be considered.

And that is really, I think, an important point, is just that it is certainly not a bad thing to have 2 options, and I have had some patients have to switch between the 2 agents due to AEs, and overall it is nice that we have options.

Next slide.

[00:44:30]

Adherence to Oral Oncology Agents

And now let us focus on adherence to oral oncology agents.

So we, of course, know that adherence is critical to achieving our desired outcomes, both from a safety standpoint and efficacy. And when you look at different studies, the reported oral chemotherapy adherence rates, and this involves a variety of agents, range from 23-100%. In general, women tend to demonstrate better adherence than men, and the reasons associated with poor adherence were found most commonly to be symptom-related distress, depression, dissatisfaction with clinical communication, and perceived burden to others.

And it is well established that reduced adherence is directly linked to increased morbidity and mortality, so, important to address adherence, identify barriers, and develop solutions are all important to the successful use of oral agents.

Next slide.

[00:45:23]

Factors Affecting Breast Cancer Medication Adherence

So here is a list of factors affecting breast cancer medication adherence, and certainly this involves our most common oral agents, are, of course, endocrine therapy, and there is a lot written about that.

So in general, the factors that are explored are age, so older patients may have a harder time, including understanding some of the complex regimens as well. For example, ribociclib being 3 weeks on, 1 week off. Lack of understanding of the treatment importance, and that could affect, for example, motivation to take the agent.

Socioeconomic status. So those who are underinsured or no insurance or have other financial barriers have higher rates of nonadherence. Adverse events are, of course, a very big one. Those who have a lot of side effects are less likely to adhere to the agents.

And then language. If instructions are not provided in the primary language, that can, of course, be a barrier.

Susan, any comments on these barriers and factors?

Susan Ogden: I think one thing I want to say about age is that it is not really listed here, but at a certain age, you have to start to weigh your quality of life. I am 76. If I have a recurrence of breast cancer, I do not know that I would go to a chemotherapy or a medicine with adverse side effects. I would really have to decide whether or not I wanted to live the remainder of my life with that.

But in terms of understanding and motivation, I really want to emphasize how important your communication is with your patient. When the patient starts the drug, if you have the staff to call the patient and ask them how they are doing rather than waiting for them to call you, that will make an enormous difference to the patient because the patient is then like, I know you are thinking about me, and you are concerned, and you want to know how I am doing. I think that would increase adhering to the treatment.

The other thing that is really enormously helpful is if I am complaining about fatigue or diarrhea, I do not want to be talked out of my feelings. I want my provider to validate them. And if my provider says something along the lines of, I know this is really hard, you know, and I want you to live a long and healthy life.

Dr Spring: So going back to the reason for why we are on this.

Susan Ogden: And it is so powerful to have your provider join with you as somebody that you care about.

Dr Spring: Great point. Thank you.

Maybe we can move on to our next slide.

[00:48:12]

Optimizing Patient Education and Adherence

So here is, I think, a helpful summary for optimizing patient education and adherence. So, kind of a bit of a checklist.

• Assess readiness to receive information;
• Ensure a caregiver is present;
• Set expectations, duration, pill burden, prevalence of AEs and outcomes;
• Deliver written information such as medication calendars, etc.;
• Provide trustworthy resources for reliable information;
• Identify gaps in education, reiterate key information;
• Work through financial concerns;
• Increase pharmacist contact and visibility, if this is a resource, of course, available in your clinic;
• Develop a process for follow-up counseling shortly after the first treatment. I think that was exactly what Susan was speaking about, calling to check in proactively if you have the resources to do so; and
• Encourage support groups if that is of interest. And then on the Decera Clinical Education website here is a link to a standardized oral agent teaching tool, and in case, help that you can check that out.

Susan, any comments on this checklist?

Susan Ogden: One thing I want to say about gaps in education and how people understand information, there is lots and lots and lots of information that is developed, and I am sure that some of the companies have developed cartoons and hand-drawn things, which can be very useful ways to educate people. So one of my surgeons, she had done her own handout with her own drawings, and it was very easy to follow. So any modification of things from clinical language into layperson's language with drawings, I think, can be very helpful to the patient, even a patient who is highly educated.

Dr Spring: Yes, and I think that also connects to something you said earlier about how much information you can take in at any one time, or especially early on when you are probably, obviously, this is maybe a new diagnosis or learning information about the diagnosis, and you can only take in so much. So to have that kind of more personalized, it is one thing to get a stack of handouts, but something that is really more curated for the patient and also is a tool that I think can help the physician in how they explain things as well. So it is helpful.

Yes, in terms of checking in with patients, I think one thing I have just noticed in our practice is before adjuvant CDK4/6 inhibitors were probably largely focused on in the localized breast cancer setting, thinking about checking in on those patients who maybe recently started chemotherapy. Now with CDK4/6 inhibitors, it is just a large group of patients on this agent. So I think having sort of a systematic approach to it, whether that means perhaps a practice nurse or pharmacist, maybe having almost a tracker of patients on these agents, and maybe having a standardized way to check in with folks also to ensure if I could maybe design, if I had all the resources in the world, to have everyone tracked and make sure the labs are happening and all that. But it has definitely evolved a lot as the population of patients eligible for these patients has, of course, increased with the approval of ribociclib as well.

All right, next slide.

[00:51:30]

Acknowledging Potential Healthcare Disparities to Promote Adherence

So here I just want to review potential healthcare disparities in terms of promoting adherence as well. So to address potential disparities in care, important to discuss the patient's satisfaction with treatments. As you heard Susan speak a bit about before, about addressing the side effects and really connecting with them about that and reminding why this treatment is important.

Satisfaction with healthcare provider communications. Of course, people want to feel understood and respected by their healthcare providers, want to be involved and share decision-making, want to build trust and confidence in their healthcare providers, and really, the better understanding they have of disease and treatment, of course, will help adherence. And this is, of course, just not something one provider can do on their own, but it is important, obviously, to have access to resources in the clinic and for patients to have a support system, including the ability to even, of course, get to appointments.

Virtual care, I think, has been very helpful in this regard. Hopefully that is something that will continue. I think it is also important for the clinic to provide help in navigating insurance claims and financial assistance programs that we spoke about before for these high-cost medications, and having a resource specialist can be really helpful for this.

Listening to and understanding each patient's goals to help develop manageable plans for achieving their healthcare goals. As we have already talked about a bit, just the important role that really everyone on the team plays. So oncology pharmacists, nurses, and patient navigators are all an integral part of oncology treatment and patient care. And really, a team approach seems to be what certainly works best to help patients with the best care.

Susan, any comments on these topics?

Susan Ogden: I think this is a really good summary of what it takes to really take care of people and ensure their adherence to these medications that can save their lives. Again, if your patient feels like you care about them, then they are going to want to please you, really. I mean, it is all about the relationship.

And just feeling understood and respected. Validating, it is very hard for people to validate sometimes because they think they are going to sort of open up something. But if I say, "Oh, this diarrhea is really, really hard," just validating, "Yes, it sounds like it is really hard." And once you validate that it is hard, then you can go on to why it is so important to continue and how much I care about you doing this.

Dr Spring: Great points. We will move on to our next slide.

[00:54:26]

InterACT Case Simulation and Discussion

Okay. So next slide.

[00:54:30]

Patient Case Continued: Woman on Adjuvant Abemaciclib With Diarrhea

So that is, again, reminding us of the case that we already reviewed.

Started adjuvant abemaciclib, had grade 3 diarrhea on the agent, so held it.

Next slide.

[00:54:42]

Poll 3: Which of the following topics related to toxicity management and adherence would you like the faculty speaker and patient advocate to discuss?

And so here is our poll. Again, which of the following topics related to toxicity management and adherence would you like us to focus our discussion on?

Several options there for you to look at, and we can open the polling.

All right. Again, lots of topics of interest. So we had a tie for C and E. So C, how we talk with patients about the importance of adherence. And then E, practice workflows that improve toxicity management and adherence.

So maybe starting with C first. So I think one thing with adherence is that, as we discussed a bit, that kind of earlier check-in, so, even with endocrine therapy alone, typically I will schedule a virtual visit a couple of months after it started to really kind of check in early about it.

I think sometimes if we wait a full 6 months, a lot can happen. I think sometimes, obviously, it is not uncommon for patients to stop, and if you are not talking to them for a while, there might be several months of not being on therapy. So I think an early check-in is something I have found.

And with the CDK4/6 inhibitors, one thing that is nice is you need to check the labs more frequently early on, and with ribociclib, doing that EKG 2 weeks in. So I use those as opportunities to have an early check-in appointment as well. And I think just being proactive about the concerns and side effects certainly helps promote adherence.

Susan, anything to add about this?

Susan Ogden: I think the other thing I would add is to be really excited about the medication because I did not really know how far breast cancer treatment had advanced until I got breast cancer 5 years ago, and it is just incredible how many different options there are. And I would bring that excitement when you are discussing it with patients because when I was growing up, we did not have these. Women had mastectomies and died without any of these treatments, and so it is just phenomenal how many breast cancer treatments there are that really extend women's lives without recurrence.

And I would bring that sense of excitement when you are talking to them. You are part of a new wave of cancer treatment.

Dr Spring: That is a great point. Actually, a lot of my patients will ask me, like, what is new? Even if it does not apply to them, they just want to hear what is happening in the field? What are you guys working on or thinking about? So I agree, really important to kind of share that excitement.

And let us see, E was practice workflows that improve toxicity management and adherence. So I think I described what my dream would be if we had the resources to really get everyone on these agents just to make sure the labs are being done and that we are checking in with people. I think we actually were able to do that early on, but then I think as we had more and more patients on these agents, it is just the numbers are huge, which, again, is a great news story that patients are eligible for these agents and that we are seeing the decreased recurrence of breast cancer, so all that is great.

It is logistically, I think, a little trickier, and so I think a lot of my patients travel a bit far to get here to Boston, so I will do a lot of virtual visits in terms of ways of making sure we are checking in and local labs as well, just to try to kind of keep it easy to be able to get those labs done.

And this is a small thing, but it is one thing if people get labs done at a satellite or a lab connected to our hospital system that those results come right to me. If you use maybe a different lab where they are faxing the results, and we still do use fax machines in 2025, that can be a lot harder to track. I do not get some, you know, notification when fax results arrive. So typically, a lot of our patients are on our patient portal, and I will tell them, "Hey, it is okay to write us a note," you know, maybe a few hours after you get your labs done, or just to make us aware so we are looking out for them too in case there was an issue with us receiving them.

And also I think just going over kind of the lab and testing schedule, and I think a lot of patients really become experts in sort of what we are looking at and what we are following. For example, explaining what we are actually looking at in the labs that absolute neutrophil count, the ANC is something obviously it is focused on a lot with CDK4/6 inhibitors, and I think it is helpful for patients to understand what is the number we are looking for, for example.

Susan, anything to add for that topic?

Susan Ogden: Just in terms of practice workflow, as much as the communication can come from your office to the patient, at least initially, either in the manner of a phone call or something through MyChart, that is going to make a difference to the patient.

Dr Spring: Yes, I think the MyChart and other patient portals have helped a lot, and that is, certainly both ways, right? It can be hard to reach people on the phone, and then vice versa, calling the clinic can obviously be hard, so I think it is great having that option.

All right, we will move on to the next slide.

[01:00:30]

Resources for Optimizing the Use of CDK4/6 Inhibitors in HR+/HER2- Breast Cancer

So here is just a list of other resources available for optimizing the use of CDK4/6 inhibitors, and there is a QR code there. And also available is an interactive tool for managing AEs with these agents are available on the Decera Clinical Education website as well.

Next slide.

[01:00:49]

A Few Final Questions

And so a few final questions.

[01:00:53]

Posttest 1: How confident are you in your ability to apply shared decision-making and communication strategies to support patient adherence/persistence on adjuvant CDK4/6 inhibitor treatment?

So posttest 1, now how confident are you in your ability to apply shared decision-making and communication strategies to support patient adherence/persistence on adjuvant CDK4/6 inhibitor treatment? And your 5 options are there.

We can open polling.

So we, I think, are better because we have much higher in the "modest confidence" and "confident" category and "very confident". So that is great to see.

Next slide.

[01:01:36]

Poll 4: Do you plan to make any changes in your clinical practice based on what you learned in today's program?

And poll 4, do you plan to make any changes in your clinical practice based on what you learned in today's program?

1. Yes;
2. No; or
3. Uncertain.

We can open polling. And we got over 50% for yes. That is great to see as well.

Next slide.

[01:02:08]

Poll 5: Please take a moment to text in one key change that you plan to make in your clinical practice based on this education.

And poll 5. Please take a moment to text in one key change that you plan to make in your clinical practice based on this education. And so you can scan this QR code to text the response. We will give everyone a moment to scan this.

All right, we can go to the next slide.

Audience Question and Answer Plus Team Discussion

Dr Spring: We can see the, yes, so then lastly, audience question-and-answer plus team discussion. I can check the Q&A. Our Decera Clinical Education team, would all questions come through the Q&A or anything on your end?

Alexander Ballard: Yes, I am asking them right now. One second.

Speaker (Decera Clinical Education): They will not be able to hear you, you have to come close. Yes, just ask the question again.

Speaker: Yes, it is a general question, the role of vitamin D in patients with breast cancer and chemotherapy?

Dr Spring: Yes, I think the literature has been pretty mixed. Certainly in this patient population, we are probably also often recommending adjuvant bone-modifying agents as well. So we know there is evidence with adjuvant phosphates in terms of reducing recurrence risk.

So not typically the setting where I am checking vitamin D, just want to make sure it is at a sufficient level before starting that agent. But overall, typically do advise patients, especially due to the endocrine therapy, to take some vitamin D. And typically for calcium, try to focus ideally on getting it from the diet for better absorption.

Speaker: What is the level when you see the blood work? Do you see, because there is a big range from 30-100, do you see a certain number, 70 is good, something like that?

Dr Spring: Oh, for vitamin D?

Speaker: Yes.

Dr Spring: Yes, our institution recently actually seemed to decrease the upper limit of normal.

So I think our normal is at least 30. I do occasionally see patients that are too high, above 100 or something like that. And certainly in those situations, you usually find out they are taking pretty large doses continuously.

So I go by our institutional range. And as long as we are in the normal range, I feel good in terms of a bone-modifying agent.

Speaker: So you say like 30 is okay?

Dr Spring: Yes, above 30 is considered normal.

Speaker: Yes, because I do not know why, in particular, this vitamin D, they put a range from 30-100. I do not know why they put that big number.

Dr Spring: Yes, that used to be ours. I think under 20 is more of a concern. But yes, I think the 30-100, I think we lowered ours because above 100 is when I think you could run into some issues. So I think we might now be 30-70 in ours.