Addressing Challenges With Adherence and Persistence to Oral Anticancer Therapies in Patients With Breast Cancer

 

[00:10:40]

 

Introduction

 

Kendall Schick (CEA): Hello, everyone, and welcome to this afternoon's continuing medical education program. My name is Kendall Schick, Scientific Director Oncology at CEA. I am pleased to welcome you to our program titled, Addressing Challenges with Adherence and Persistence to Oral Anticancer Therapies in Patients with Breast Cancer.

 

This program is supported by educational grants from AstraZeneca and Merck Sharp & Dohme, LLC.

 

[00:11:09]

 

Program Co-Chairs 

 

I would like to introduce tonight's program chairs: Kristi Orbaugh and Kimberly Podsada.

 

[00:11:16]

 

Disclosures 

 

Their disclosures are listed here and also available in the downloadable slide set.

 

[00:11:22]

 

Learning Objectives 

 

Also available in the downloadable slide set are the learning objectives for tonight's program.

 

[00:11:28]

 

Outcomes Analysis: What Did You Learn?

 

Before we begin, we will be asking some baseline questions, which will be repeated at the end of the program in order to measure the educational impact of the program. During the program, you will be allowed to submit Q&A questions and interact with our speakers via the Q&A chat at the bottom of your screen. Let us get into some pre-program questions then.

 

[00:11:50]

 

Your Virtual Platform: Polling and Questions

 

In order to answer the pre-program questions, there will be a prompt on your screen and please interact there.

 

[00:11:57]

 

A Quick Survey

 

Poll 1

 

Polling question one. How many people with breast cancer do you provide care for in a typical week? Is it:

 

1. 1 to 4;
2. 5 to 10;
3. 11 to 15;
4. 16 to 20;
5. More than 20; or
6. Not applicable.

 

Close the poll.

 

[00:12:35]

 

Poll 2

 

For our second polling question, which best describes your practice setting? Is it:

 

1. Academic; or
2. Community practice setting.

 

Close the poll.

 

[00:12:56]

 

Pretest 1

 

With that, I would like to hand the mic over to our first speaker, Kristi Orbaugh.

 

Kristi Orbaugh (Community Hospital Oncology Physicians): All right. For our pre-test questions, we would like for you to answer these for us. Which of the following strategies would be most effective in helping your patient improve adherence to her prescribed therapy?

 

1. Provide additional education on the importance of adherence;
2. Recommend that she or he join a support group;
3. Utilize reminder systems and adherence monitoring tools; or
4. Educate her or him on the risk of non-adherence.

 

It looks like most of you chose number C. We will talk more about these test questions pre and post. We will chat about those later.

 

[00:14:15]

 

Pretest 2

 

Question number 2. Which of the following adverse events commonly associated with the addition of capivasertib to endocrine therapy would be important to discuss with your patient with hormone-positive metastatic breast cancer who is considering a new treatment alternative.

 

1. Diarrhea;
2. Interstitial lung disease;
3. Keratopathy;
4. Peripheral neuropathy.

 

Okay. Diarrhea and peripheral neuropathy are almost neck and neck. Well, I guess most of you chose diarrhea.

 

Okay, the next question.

 

[00:15:37]

 

Pretest 3

 

When counseling a patient with estrogen receptor-positive/HER2-negative breast cancer with an ESR1 mutation before receiving elacestrant, which initial strategy would you recommend to mitigate nausea and to improve adherence to the therapy?

 

1. Take elacestrant on an empty stomach;
2. Take elacestrant with food;
3. Schedule with an antiemetic 30 minutes before each dose;
4. Initiate therapy at a low dose and then ramp up the dosing to full dose.

 

Okay. It looks like most of you said schedule an antiemetic 30 minutes before each dose. Again, we will go over the correct answers later.

 

[00:16:59]

 

Pretest 4

 

Here is number 4. Your patient with triple negative breast cancer and a BRCA1 pathogenic variant will be initiating adjuvant olaparib. Given the potential toxicity, which of the following supportive medications should your patient have available?

 

1. Cetirizine;
2. Ondansetron;
3. Metformin; or
4. Prednisone.

 

Those supportive meds are important, aren't they? Okay then, let us see what our poll shows. Most of you say ondansetron. All right, our next 1.

 

[00:18:04]

 

Setting the Stage: Understanding Adherence With Oral Oncolytics

 

That concludes all of our pretest. Now what we are going to talk about is let us just set the groundwork for adherence, specifically with these oral oncolytics.

 

Now, tonight we are going to be specifically talking about the use of oral oncolytics within the breast cancer population. But just to give you an overview on how important this topic is, the NCCN has stated that in May of 2025, approximately 400 new oncology medications are in the pipeline. Of those 400 medications, about one fourth of those or a 100 are oral medications. That just really was very eye-opening to me and made me think just about the importance of these oral drugs, and how we are going to be using them more and more and more.

 

We will be covering several of them. Numerous oral medications for treating both early and advanced breast cancer are available, and we will cover these today:

 

• The SERMs;
• The SERDs;
• CDK4/6 inhibitors;
• The PARP inhibitors;
• HER2-targeted TKIs;
• PIK3CA-targeted therapy;
• AKT inhibitors; and
• mTOR inhibitors.

 

You can see we have got a busy 90 minutes.

 

[00:19:50]

 

Adherence to Oral Oncology Agents

 

Now, when you think about adherence, I will be honest with you, I understand why maybe patients can think maybe this pill is not quite as important as the chemo I received. Right? There just seems to me more importance in getting an IV medication as opposed to an oral medication. That really drives home the importance of making sure that we are saying to patients and educating them this pill that you are taking is just as important, and in many cases, the backbone of your treatment regimen.

 

Helping them understand that and helping them understand that staying on that medication on a regular basis, taking it as prescribed, really helps us reach the desired outcomes for that patient, both from a safety perspective and just as importantly from an efficacy perspective.

 

Now it has been reported, depending on what study you read, that oral chemotherapy adherence rates can be as low as 23%. Some even say you can find people that are 100% adherent. I will be honest with you, I have been in practice a long time, and I have not had that patient that has been a 100% adherent yet.

 

What is interesting, I guess it should not maybe surprise us, women demonstrate better adherence than men. I know that hopefully that does not rub any men on the program the wrong way.

 

Another thing that really can alter whether a patient is adhering to or not is what are the symptom related distress? What are the symptoms? Is the patient distressed? Are they depressed? Are they dissatisfied with the communication that they are having with their clinical team? What is the perceived burden to others when they do not adhere or they have poor adherence?

 

Reduced adherence is directly related to and can be linked to increased morbidity and mortality. Regularly assessing these adherence and identifying barriers, but more important, developing solutions is really, really important. We want to set these folks up for success.

 

[00:22:41]

 

Adherence and Compliance Start Where Life Happens…

 

I actually saw this quote in a magazine I was reading regarding oral adherence. When we are thinking about adherence or the old time term, compliance, it really starts where life happens. Where does life happen for those patients, and that is in their home.

 

Now, you think about it, I am not sure if we have any infusion nurses on our program tonight or not. But you think about it, if you worked today and you gave medication, you know that it went the right route, the right time, you gave it to the right patient on and on and on. But when we send those drugs home with the patient, those pills that we ask them to take, that safety net of a healthcare provider being right there, administering the drugs is no longer there.

 

[00:23:44]

 

Oral Targeted Therapy Adherence Considerations

 

Some things that may affect adherence can be the pill burden. How many do they have to take at a time? What is the dosing schedule? Do they have to take it every 3 hours, 2 times a day? What exactly does that look like?

 

How clear are those administration instructions? I know we all cringe when we tell people that they have to take something on an empty stomach, right? Because that is an hour before, or 2 hours after a meal, and that can be cumbersome. What are the drug to drug interactions? Not only drug to drug, but food interactions. When I say drugs, I am also talking about supplements and herbs and all of those things that sometimes patients take on their own.

 

Then there is what are the adverse events and how frequently do those folks have to be monitored?

 

[00:24:47]

 

Factors Influencing Adherence

 

Now, when we think about those patients, what is their support system? I know nothing makes me happier than when I walk in to do a patient teach. You see a loved one, a family member, a support person right there, taking notes. You know that that person is going to be very supportive and encouraging and helping that patient stay on. That is what we need to do too.

 

Helping patients stay on and stay adherent to their medications requires that their provider, their healthcare team, lean into that patient and understand what works for them, right? Because 1 size does not fit all. Let us look at those therapy-related side effects.

 

If we do not manage therapy-related side effects, I guarantee you patients are going to manage those at home. That might include not taking their medication to reduce the side effects.

 

Disease-related healthcare, their healthcare system as well. When you study adherence, what you will find is at the top of the list of the reasons why patients are not adherent is lack of education. I do not mean their education as in going to school. I mean, lack of understanding of why it is important. That really falls on our shoulders to make sure they understand the importance and they understand how to take it.

 

Education is not 1 and done. We do not just take it, educate the patient and then say, well, we told them about that. This is something that we do every time they come in. We have got to set them up for success.

 

A lot of patients can have a high copay. So making sure that we are really working through all that, getting them helps with grants, free drug, assistance from the pharmaceutical companies is really, really important.

 

[00:27:15]

 

Optimizing Education: The Patient Perspective

 

Okay. Optimizing that education, making sure that the patients are ready and making sure we have answered their questions, because they are not going to hear what we are saying unless we have answered all of their questions. Then not only do we verbally educate them, but also help them with written information. Part of that is going to be making sure that we are giving them written information in their language of origin.

 

We also need to make sure that what we are giving them is at a readable level. Everybody is going to call Dr Google. We all know that. It does not matter where we are in the United States, patients are going to call Dr Google. We need to help them with legitimate websites, good websites that will give them valuable information to also support the education that we have given them.

 

Then help them with calendars or alarms or whatever works best for them to help them through that. I know a lot of people are very tech savvy, and so they like to set alarms on their phone or things such as that. I kind of like my old paper calendar. They still make them by the way. I just like to take a little pen and I check when I have taken my medication. I know that sounds silly, but that is what works for me. So understanding and knowing our patients so we can help find an avenue that helps them be adherent.

 

[00:29:05]

 

Interventions to Improve Adherence

 

Making those regimens as absolutely as simple as possible. Then those clear, clear instructions, and as we said, make them patient tailored. I always like to ask patients too, when they come in and I am seeing them, let us just say my patient's name is Kimberly. I am saying that of course, because that is my co-presenter. Kimberly comes in and I say to her, “Now, in the last month, how many times have you missed your medication?” And she gives me an answer, okay. “Now, on those days, what happened? Did the alarm not go off? Did daycare call and you had to go pick up a child?”

 

Just walking through those scenarios, so hopefully we can find a backup plan if that type of thing happens again. We talked about this earlier, but making sure that they are understanding the importance of that pill. It does not matter how good a medication is, if it is in the bottle and not in the patient. Giving them that motivation and then encouraging them when they come back in.

 

[00:30:21]

Measures to Increase Oral Oncology Treatment Adherence

 

Calendars, medication checklist, pill boxes, keeping medication in a visible area, whatever works best for patients. Maybe setting alarms like we talked about. There are actually glowing pill boxes and text messages that can be sent. All kinds of programs out there, if you will, multi-component programs that really help us keep those patients on schedule.

 

[00:31:07]

 

Endocrine Therapies

 

Now hopefully we are all good with the importance of adhering. Now let us move on to our endocrine therapies. We will be talking about SERM, or selective estrogen receptor modulators. We will be talking about aromatase inhibitors, SERDs or serum estrogen receptor downgraders, and CDK4/6 inhibitors. So put your seatbelts on.

 

[00:31:45]

 

Selective Estrogen Receptor Modulators

 

Okay. When we are thinking about SERMs, really the 1 that we are most familiar with is actually tamoxifen. This date blew me away. It has been FDA approved since 1977. If you really think about it, tamoxifen is probably really the first targeted therapy we used in oncology. We use it for breast cancer treatment. Then later, it also received its approval for breast cancer prevention.

 

Raloxifene is a SERM, but it works to treat postmenopausal osteoporosis. Now, 1 real quick thing I do want to tell you about tamoxifen is how SERMs work is in certain tissues within our body, they act or mimic estrogen-like behavior, which is 1 reason why sometimes you can put patients that you are treating for their breast cancer, and they may have some baseline osteopenia, and you may see some improvement in that osteopenia because that there is estrogen-like activity with those osteoclast and osteoblast.

 

But then in other tissue within the body, it acts as an inhibitor, like in the breast cancer or in the breast tissue, it inhibits estrogen-like activity. It really works in 2 very different ways, depending on the tissue in which it is working.

 

[00:33:37]

 

Most Common SERM-Related Toxicities

 

Most common side effects are hot flashes. Anytime we try to modulate the hormonal system, we can get hot flashes, right? Leg cramps. Leg cramps can be very bothersome to those folks on tamoxifen. It is always a challenge sometimes when they are bothered with that. Blood clots, cataracts, vaginal discharge, vaginal dryness. We also want to make sure that we are watching anyone that is on tamoxifen needs to see their GYN on a regular basis because they need to be watching for increased uterine thickening. Then any mood changes as well.

 

[00:34:30]

 

Aromatase Inhibitors

 

Aromatase inhibitors. We typically use these in postmenopausal women or premenopausal women who are on a gonadotropin releasing hormone.

 

Aromatase inhibitors. What happens when we are postmenopausal is, in women, our body still continues to make some estrogen, but not from our ovaries, right? Our adrenals kick out something called androstenedione. After several metabolic steps, androstenedione becomes estrogen. The last step before it becomes estrogen, aromatase is added.

 

When we block the aromatase, theoretically we are blocking the ability to make estrogen at all in a postmenopausal woman. There are currently 3 on the market. Two are what we call non-steroidal aromatase inhibitors, and they compete with androstenedione for the binding sites and inhibit that conversion of androgens to estrogens and then steroidal AIs.

 

They bond with that aromatase enzyme and inactivate it and prevent the estrogen from being made.

 

[00:36:00]

 

Most Common AI-Related Toxicities

 

When we are looking at those types of toxicities from AIs, musculoskeletal symptoms, some women can have a lot of joint discomfort in arthralgias and myalgias, menopausal symptoms. We do have a higher risk for osteoporosis. We also have a higher risk for elevated cholesterol, cardiovascular issues.

 

With that in mind, we want to make sure that if they already have a cholesterol issue, we are reaching out to their primary care and letting them know that they will be starting on an AI. We will also watch liver functions. With any of the endocrine therapies, it is not unusual to see headache.

 

[00:36:51]

 

Managing Treatment-Related Hot Flashes in Women With Breast Cancer

 

What do we do for these hot flashes? I wish I could see you on and have you raise your hand if you have ever experienced hot flashes. There is really only 1. There is a newer drug on the market that has gotten a lot of press recently, and that is fezolinetant, and it is an NK3 receptor agonist. It has given orally, and I have had a lot of patients really benefit from it.

 

Unfortunately, it can be a little pricey if they do not have good insurance coverage. So you want to make sure that you are working with them on all of that. Also off-label indications, the SSRIs have been used, as have SNRIs, gabapentin, oxybutynin, clonidine. All of those have been used. Some with success, some with not. It has been my experience, it is just very individual to the patient.

 

Dietary supplements. We will also see occasionally patients try hypnosis, biofeedback, that type of thing. Again, some find it beneficial, some do not.

 

[00:38:20]

 

Oral SERDs

 

Oral SERDs.

 

[00:38:21]

 

Safety of Oral SERDs

 

There is only 1 on the market right now, and it is elacestrant.

 

[00:38:28]

 

Safety Summary of Approved and Emerging Oral SERDs

 

When we work with elacestrant, the number 1 toxicity that we can see is some nausea.

 

[00:38:37]

 

Elacestrant Dose Modification Recommendations for AEs

 

What we would do with those folks that have nausea is we are going to tell them to try to take it with food that is really important. That will decrease their nausea.

 

[00:38:54]

 

Emerging Supportive Care Strategies: Recommended Monitoring With Elacestrant

 

Then it can also cause some hypercholesterolemia about in 30% and hypertriglyceridemia in about 27%. We want to make sure that we are following those lipid profiles along.

 

[00:39:10]

 

CDK4/6 Inhibitors

 

Now, CDK4/6s.

 

[00:39:13]

 

CDK4/6 Inhibitors

 

There are currently 3 on the market that are approved for metastatic:

 

• Palbociclib;
• Ribociclib; and
• Abemaciclib.

 

These drugs have been with us for about 10 years. Palbociclib was the first 1 released. How they work is they inhibit phosphorylation of Rb protein. What this does is it deactivates a tumor, which deactivates the tumor suppressor protein, and this prevents cellular proliferation. That is the last thing we want in a cancer cell is to proliferate.

 

There are also 2 of them on the market, ribociclib and abemaciclib, that have been moved into that adjuvant setting for patients who have high risk of recurrence.

 

[00:40:13]

 

CDK4/6 Inhibitor Dosing/AE/Monitoring Considerations

 

Okay. Now, just when you are thinking about adherence and all and how drugs are to take. Abemaciclib is 1 pill taken twice a day. Does not matter if you take it with or without food. Palbociclib 1 pill but a little more complicated regimen, maybe 21 days on, 7 days off, whereas abemaciclib is daily.

 

Ribociclib is 3 tablets in metastatic disease, 2 tablets in early disease. This is also on once daily for 21 days on, 7 days off. For those we would want to help with calendars and such until they get the hang of that 21 days off and then 7 days’ vacation, if you will.

 

Now, when we are working with these drugs, some of the more common side effects that we can see. We are going to monitor blood counts. We are going to monitor liver functions. Specifically with abemaciclib, we can see venous thrombotic events that we do not necessarily see with the others. With ribociclib, we can see QT prolongation that we do not see with others.

 

What that says to us is we just need to know the drug that the patient's on and make sure that we are monitoring appropriately.

 

[00:41:48]

 

Dosing Considerations for Adjuvant CDK4/6 Inhibition in Early Breast Cancer

 

Another thing that is very, very important is making sure that we know all the medications that patients are on, right? Because there can be drug-to-drug interactions. There can also be interactions with supplements, over-the-counter medications, that type of thing.

 

[00:42:12]

 

Key AEs With CDK4/6 Inhibitors: Monitoring and Prevention

 

When we are looking at the most common toxicities we see, diarrhea, then we are going to follow liver functions along, we can see neutropenia, venous thrombotic events like we talked about, ILD and QT prolongation. Let us delve a little bit deeper into a couple of those that are a bit more prominent.

 

[00:42:36]

 

Diarrhea Prevalence With CDK4/6 Inhibitors

 

When we are talking about diarrhea, with abemaciclib, about 83% of those folks on abemaciclib will have some sort of diarrhea as opposed to about 35% of the people on ribociclib, if the patient is on abemaciclib. The diarrhea is worse within the first 8 weeks, and you will see that depicted on this graph.

 

The important thing to remember is it is worse in those first 8 weeks. We have got to really walk very closely along with the patient so they know what to do. They need antidiarrhea medications at home.

 

[00:43:20]

 

Neutropenia Prevalence With CDK4/6 Inhibitors

 

They need to know when to start them. Also specifically with abemaciclib and ribociclib, there are dose adjustments that we can do. We need to remember that the dose we start at with any of these drugs, abemaciclib or ribociclib, may not be the dose that we stay at because the idea is to keep people on dose.

 

Neutropenia can also be seen. We see this more with ribociclib, about 94% compared to only 46% with abemaciclib, and about 80% with palbociclib. We are going to make sure that we are monitoring those counts really well.

 

[00:44:04]

 

Managing Neutropenia With Adjuvant CDK4/6 Inhibitors

 

We are going to monitor CBCs and CMPs before we start, and then every 2 weeks for the first 2 months, and with abemaciclib just for 2 more months, monthly after that ribociclib, we are going to follow them along monthly for 4 months. Just a couple more months of following those counts with ribociclib, simply because we can see a bit more neutropenia with that.

 

The big thing that is important when we are talking about any toxicities is making sure that we are monitoring them and grading them so we can then look at dose modifications and modify those doses appropriately.

 

[00:44:54]

 

Summary of ILD From CDK4/6 Inhibitors

 

Now, ILD in any of CDK4/6, it has been reported with all 3. It is very, very rare. We are talking less than 5% in any of them, but it is something that we need to watch out for. So understanding the patient's baseline pulmonary symptoms are very, very important. Do they smoke? Have they had chest radiation? All those types of things are very important, so we can respond appropriately.

 

[00:45:33]

 

Hepatotoxicity

 

Hepatotoxicity, you can see it. I alluded to how we are going to watch these folks along. It is rare that we see grade 3/4 hepatotoxicity with either abemaciclib or ribociclib or palbociclib. But it is important to monitor them along. Again, to repeat how we are going to follow these with abemaciclib, we are going to check CBC and CMP every 2 weeks for the first 2 months, and then monthly for the next 2 months. Then as clinically indicated.

 

For ribociclib, CBC and CMP every 2 weeks for the first 2 months, and then monthly for the next 4 months, then as clinically indicated. Again, remembering we may have to hold doses, we may have to reduce doses, and that is okay. The goal is to keep the patient on therapy.

 

[00:46:37]

 

Drug–Drug Interactions Among CDK4/6 Inhibitors

 

Finally, when we are talking about the drug-to-drug interactions, I alluded to this earlier. All 3 of these drugs are metabolized via that CYP pathway, which is so common. It is a very common hepatically metabolic pathway. We have to know everything patients are on.

 

In my area, I have a lot of patients that take things that maybe are not on their list to take or take things over-the-counter or supplements or herbs or all kinds of things. It is really important that we know exactly what they are taking.

 

[00:47:27]

 

Interactive Tool for Managing AEs With CDK4/6 Inhibitors

 

CCO has a beautiful interactive tool for managing AEs with the CDK4/6s, and we will give you information on how to get that.

 

[00:47:38]

 

Skill Building and Feedback II (ARS/Case Discussion): Class-Specific Barriers to Adherence and Persistence, Patient Counseling, and AE Management

 

Now, skill building. I will go through this case. We will go through it quickly, and then Kimberly and I will discuss how we manage things. But I encourage you all to end the questions and answers. If you have a really good way that you manage a pearl that you would like to share with us, we would appreciate that. We all are here and we want to learn from each other. We are very anxious to hear some strategies you might use to manage toxicities.

 

A premenopausal 42-year-old woman with high-risk breast cancer being managed with a gonadotropin releasing hormone agonist plus letrozole, so an aromatase inhibitor, and abemaciclib in the adjuvant setting. The patient develops grade 2 diarrhea after the second week on this regimen. After a few months, she develops a grade 2 fatigue and is having annoying hot flashes.

 

Number 1, how would we manage her diarrhea? That is first off, because we have to keep her on drug, right? We want to manage that diarrhea so she is not running to the bathroom all the time. Then fatigue that really alters your quality of life. How is that managed? Please shoot us your recommendations or things in the question and answer.

 

Kimberly, I am anxious to hear from you, what do you do with diarrhea for your patient?

 

Kimberly Podsada (University of California): Well, very much like you already reviewed very well, thank you for that. With the grade 2 diarrhea often when you are looking at the PI, it does not always say that you have to do anything about a grade 2 diarrhea. However, there are always situations where you need to just listen to what the patient is saying, and you can calculate it. I can calculate it and say, based on what they are reporting, it is only a grade 2, and according to the PI, I do not have to do anything.

 

But if the patient is telling you that they are bothered by this, it is interfering their function, then of course we are going to do something. I am going to want to make sure that they are aware of taking Imodium and how are they taking Imodium. I also want to reassure her that we tend to find that the diarrhea is fairly, you have to manage it pretty proactively within the first 8 weeks, and then it tends to decrease over time.

 

But I have found many of my patients on abemaciclib, will just take a daily Imodium, and that is the pattern that works for them, but they have to get to that point. It is really based on the individual also. But are they using the prophylactic tools? How are they using them? Start to talk maybe about their nutrition even.

 

Kristi Orbaugh: Okay. Now let me see. We got a comment on the chat. Sounds like a lot of people use Imodium for the diarrhea. Fatigue, someone has recommended B12 injections or oral iron and that might be appropriate if they are iron deficient or B12 deficient. Certainly that absolutely might be appropriate.

 

Kimberly, I will tell you, fatigue from these medications, it is tough. I sometimes just really scratch my head and I do not always have a good answer for these patients. We talk about sleep hygiene. We talk about managing your energy and all that. What do you talk to patients about?

 

Kimberly Podsada: Well, for this particular patient, I am looking at the whole situation and she has hot flashes. Are they interrupting her sleep? Is she not getting good sleep? Is that contributing to fatigue? I feel like the new drug that is on the market for hot flashes, VEOZAH or fezolinetant. Is that what we decided it was?

 

Kristi Orbaugh: Yes.

 

Kimberly Podsada: Anyway, it has been really successful. Many insurances want you to have failed something first. Paroxetine was actually prescribed and was on the market at a low dose, 10 mg for hot flashes. I do tend to use a lot of the low dose antidepressants. If they have nerve pain, if they have hot flashes, if they have trouble sleeping, then I am using gabapentin, and I just encourage them to increase activity as much as they can because exercise tends to really help with this whole symptom set.

 

Someone also mentions here about dehydration. Absolutely. If you have diarrhea and you are dehydrated, it is just a vicious cycle. How about you?

 

Kristi Orbaugh: Absolutely. I do love some of the strategies that you mentioned. Patients that are having a lot of those leg cramps and are not sleeping well and feel fatigued. I have had some good luck with using gabapentin at bedtime, and that tends to help mitigate some of the hot flashes as well.

 

Well, Kim, thanks for helping us with this. I just turn it all over to you.

 

Kimberly Podsada: Okay. Let us move on here. I think there is a conclusion slide for you.

 

[00:54:11]

 

Conclusions

 

Kristi Orbaugh: Sure. I am getting lazy on the job. I just want Kimberly to take over right away. Well, yes, there is a conclusion. We talked about the CDK4/6s. Remember, there is indication for 3 of them for metastatic disease: abemaciclib, ribociclib, and palbociclib. When we are talking about early breast cancer, using them adjuvantly in those patients that have certain risk factors. Abemaciclib and ribociclib have the indication.

 

CDK4/6s have very specific toxicity profiles. Some are a little different. All of the CDK4/6s do not have the exact same toxicity profile. Number 1, we need to be familiar with the drug so we can help prepare the patient for what toxicities they might have remembering the importance of education. If you do not remember anything else from my portion, please remember educating our patients is not a 1 and done. It is an ongoing process from the day we meet them until our last interaction with them, we need to always be trying to educate our patients.

 

Remembering that those AEs can have a negative impact on quality of life. If we do not manage the toxicities, patients are going to manage them on their own. Oncology nurses need to be vigilant about monitoring these toxicities and being prepared to manage them.

 

Many times I think that the nurses will hear more about the toxicities sometimes than the providers. Oncology nurses are right there on the forefront, the main line, if you will. Now you can take over, Kimberly.

 

[00:56:22]

 

PARP Inhibitors

 

Kimberly Podsada: Thank you, Kristi. I am going to start talking about some of our other targeted therapies.

 

[00:56:31]

 

Approved PARP Inhibitors in BRCA-Mutated Breast Cancer

 

I will of course mention along the way some of my concerns regarding adherence, whether that is due to pill burden or whether that is due to toxicities. First of all, the 2 PARP inhibitors I am going to review are olaparib and talazoparib.

 

First of all, you need to have an FDA approved companion diagnostic test that demonstrates that you have a BRCA mutation. In the olaparib clinical trials, it was actually studied for metastatic and for the adjuvant setting. Very much like the CDK4/6 inhibitors that Kristi was talking about, we are seeing a lot of these drugs move into the adjuvant setting as well, and also have a really good benefit for our patients that are considered high risk.

 

Olaparib has taken 300 mg twice a day with and without food. In the adjuvant treatment, it is for adult patients with our deleterious or suspected deleterious germline BRCA-mutated HER2-negative high-risk early breast cancer who were treated with neoadjuvant or adjuvant chemotherapy. These are hormone positives or our triple negatives.

 

Then it is also same dosing for the metastatic setting. In the metastatic setting, patients are staying on this therapy until unacceptable toxicity or disease progression. In the adjuvant setting, they are taking it for 12 months. Also in the adjuvant setting, what is important to think about are we are really giving it to a specific patient population who are at high risk. In the adjuvant setting clinical trial, we did see a clinically meaningful overall survival as well as a disease risk reduction of recurrence. So it is making a difference in the adjuvant setting.

 

Although I am not going to go into too many details about the clinical trials, please know that we are talking about these therapies and recommending these therapies because it has shown to be better than that standard of care or chemotherapy. It is also allowing patients to stay on oral therapies before needing another line of chemotherapy.

 

Talazoparib is 1 mg once a day with or without food, again, needing to have that germline BRCA-mutated FDA-approved companion diagnostic test.

 

[00:59:11]

 

PARP Inhibitors: MoA

 

I am going to do a very simplified version of a PARP inhibitor mechanism of action. This is important for me to understand because when I explained this to my patient, Kristi was really, really, really good at making sure we are educating our patients. Sometimes I will let them know about the mechanism of action as well. I will give them visuals maybe to think about adherence and why they are on something and why a medication is working.

 

If you think about this BRCA mutation, it is something that is genetically passed on to an individual. This is in their DNA. There is a mutation that the body is constantly repairing. PARP genes encode for this enzyme that help to maintain DNA integrity. If you imagine that you have got this mutation in your DNA and PARP is constantly coming in and repairing it like its normal job, because it sees it as being something normal.

 

This damage is constantly being repaired. By applying a PARP inhibitor, we are stopping that process. We are stopping that mutation from continuing to proliferate. This then causes apoptosis for these breast cancer cells in patients who are BRCA positive. That is my simplified version.

 

[01:00:52]

 

Differences Between Somatic and Germine Mutations

 

When we think about our mutations, we are looking at germline or somatic mutation. The germline is where it is inherited, mom or dad or grandmother or grandfather. It has been passed down through the family, whether or not those individuals actually had breast cancer or other cancers, you have a 50% chance of getting this mutation. Just because you have the mutation does not mean that you are going to have a breast cancer and other cancer, but you are much higher risk of it happening.

 

Then we have our somatic mutations and these are acquired. This is the actual cancer cell itself that becomes mutated and acquires this mutation. It is important to always constantly be thinking about repeat testing to see if there are new targetable mutations that are available for these therapies.

 

[01:01:54]

PARP Inhibitors: Tolerance Profiles of Olaparib and Talazoparib

 

Looking at some of the PARP inhibitor AEs that grade 3 AE is really where you are going to need to intervene and help your patient manage this. We have the abnormal labs, especially anemia. Anemia is going to be significant, which then may contribute to fatigue as well. We have to think about maybe giving our patients some tips and tools on how to manage fatigue. Anemia, we are going to catch by blood work, which we are going to be doing frequently.

 

Also, both of these PARP inhibitors had neutropenia and thrombocytopenia. Labs are going to be done regularly, typically monthly, and as indicated. Now, MDS and AML were seen using these PARP inhibitors for the olaparib studies, there were no signs of MDS or AML, but if you find that your patients’ counts are not recovering well, you are continuing to run into issues, you may want to have a hematologist consult.

 

For all grades nausea, you can see both PARP inhibitors are going to have nausea as something that we also need to help manage, and alopecia as well, although alopecia was more of a grade 1 with just some hair thinning.

 

[01:03:26]

 

Managing GI Toxicity With PARP Inhibitors

 

GI toxicity is probably 1 of the main concerns with the PARP inhibitors. Even with mild nausea and vomiting, this may affect the patient's adherence because it does impact the quality of life. But nausea and vomiting tend to diminish over time. Using prophylactic medication usually in the beginning is very helpful. Letting them know that they may want to take an antiemetic before each PARP inhibitor and twice a day with olaparib.

 

You want to avoid aprepitant with olaparib because, again, we need to know those other drugs and the interactions. You can also recommend taking PARP inhibitor after meals to reduce nausea as well. It is not likely that they are going to have severe nausea and vomiting, so you do want to be thoughtful about working up other things if this continues. Then, of course, other GI toxicities, constipation, diarrhea, and abdominal pain.

 

[01:04:31]

 

Managing PARP Inhibitor–Associated Nonhematologic Toxicities

 

As with many grading and trying to figure out how to best help patients manage toxicities that grade 1, grade 2, sometimes you do not need to intervene, but maybe you want to look at nutrition, make some recommendations. For those grade 2s, you may need to hold their dose or dose reduce.

 

[01:04:55]

 

Recognition, Prevention, and Management of Common AEs Related to PARP Inhibitors

 

Again, when we looked at some of the AEs here, we can see abnormal labs are very common with both PARP inhibitors that nausea, anemia, and fatigue as well. These are things that may be challenging for your patient to adhere to the medication regimens.

 

[01:05:15]

 

Skill Building and Feedback II (ARS/Case Discussion): Class-Specific Barriers to Adherence and Persistence, Patient Counseling, and AE Management for PARP Inhibitors

 

For this patient, Kristi and I are going to discuss a 36-year-old woman who was diagnosed with high-risk, early-stage, BRCA1, left breast cancer, who completed all of her chemotherapy, underwent bilateral mastectomies, radiation, and then she started on her GnRH agonist injections monthly with her anastrozole and olaparib twice a day.

 

She and her husband have 2 children. They are young, 3 and 6. She works part-time, he works full-time and she is reporting bothersome fatigue and nausea and admits to occasionally missing her second dose of olaparib.

 

First of all, what are some of the other symptoms we might work up and how are we working up her symptoms, like looking at those labs? What interventions would we consider and how would we advise her to consistently take her scheduled doses of medications? Do not forget that you can use the question and answer box if you want to add your 2 cents, which we would appreciate.

 

Kristi, what do you do in this situation? We only have a couple of minutes, but I would love to hear your take on this.

 

Kristi Orbaugh: We hit earlier on the fatigue and such, and obviously the last thing we want her to do is to miss any pills, right? If we can avoid that. Maybe even scheduling antiemetics, so she is taking them regularly and hopefully that would mitigate some of that.

 

Kimberly Podsada: Thank you, Stephanie, for writing in. She thinks this woman needs a nanny. Yes, she needs more support for sure. We have to look at the whole patient and she is busy. Her husband is busy. We want to help her make sure she can stay on this therapy. Again, it has demonstrated overall survival. She is high risk. It is demonstrated reducing the risk of disease recurrence.

 

We have to think about what is going to work best for her and incorporate some of the tools that Kristi discussed.

 

Kristi Orbaugh: Kimberly, when we are working up her symptoms, take away her breast cancer, okay, forget her breast cancer and look at where she is in life. She is fatigued anyway, most likely. We also have to make sure that when we are setting with patients and we are really assessing them, sometimes we have to pull away the noise. Part of that may be, just helping her maybe understand better energy conservation strategies and such. The poor gal, she has got a lot of balls in the air and she would be tired whether she were taking medications that could make her fatigued or not. So helping support her through that.

 

Kimberly Podsada: Yes, and Dorothy also mentions here that sometimes the psychology of a patient feeling like they are a burden, it can be very overwhelming. We need to encourage her as well as other patients to really allow friends and family to help and setting an alarm also on her phone or something for that having to take a medication twice a day.

 

I am going to move on. Thank you.

 

[01:09:10]

 

HER2-Targeted TKIs

 

I am going to talk about the HER2-targeted TKIs, or tyrosine kinase inhibitors.

 

[01:09:17]

 

Approved HER2-Targeted TKIs

 

We have 3 that are currently approved for HER2-targeted TKIs in the breast cancer world. Neratinib, again, is used in the adjuvant setting as well as the metastatic setting. One of the challenges that people may have with neratinib is it is 6 pills, but it is only once a day. It usually is with their endocrine therapy as well. In the metastatic setting, it is also taken with capecitabine, which also can be pill heavy.

 

Neratinib is taken daily, whereas capecitabine is taken for your 2 weeks on and 1 week off. Definitely need to make sure patients have resources to remember that schedule.

 

Tucatinib is given with trastuzumab and capecitabine, and this is for HER2-positive breast cancer, including brain mets for those patients who received 1 or more greater lines of HER2-targeted therapies. This medication is given twice a day, but the capecitabine is also given twice a day. Those 2 medications can be taken at the same time. Remembering that capecitabine is still 2 weeks on and 1 week off, and tucatinib is daily.

 

Then we have lapatinib. It is also approved in the metastatic setting and it is used with capecitabine as well, or it is used with letrozole. Again, we need to think about some of the pill burden here, especially for lapatinib, which also is 6 pills at once as well.

 

[01:10:59]

 

HER2-Targeted TKIs

 

Simplified graft here, really showing you the targets of each of these TKIs. You can see here that the neratinib is hitting several HER receptors. We have 4 HER receptors and neratinib is hitting the majority of them, which is known to potentially increase some of the side effects that it has. Whereas lapatinib and tucatinib are very highly specific and have less side effects than the neratinib does.

 

[01:11:35]

 

Pharmacology of HER2-Targeted TKIs

 

There is also different inhibitions. Lapatinib and tucatinib are also reversible as well as more highly selective than neratinib. But the neratinib is also the only 1 that has been approved in the adjuvant setting. Again, watch what other drugs that your patient is taking because it is also metabolized by the CYP3A receptor in the liver.

 

[01:12:01]

 

Recognition, Prevention, and Management of Common AEs With HER2-TKIs

 

All 3 of the TKIs, we need to pay attention to diarrhea, nausea, vomiting, fatigue sometimes rash, sometimes mouth sores. We need to rule out other possible causes of diarrhea. We want to be aggressive with our antidiarrheals as scheduled or as needed.

 

Loperamide, Lomotil, budesonide, colestipol followed by potential dose reduction as needed. Also there is a really interesting study called the CONTROL study, where it looked at dose escalation of neratinib. This has really helped to mitigate some of the diarrhea for patients with neratinib.

 

[01:12:49]

 

Considerations for Management of Neratinib-Induced Diarrhea: Prophylaxis

 

Considering our management of diarrhea, we can do that dose escalation, which has been very helpful. We can start off immediately with the loperamide. You can have patients just start automatically taking it and not waiting till they have diarrhea. Then we also want to think about doing dose reductions, if we need to as well or permanently discontinuing for grade 4 diarrhea or more.

 

[01:13:22]

 

Skill Building and Feedback III (ARS/Case Discussion): Class-Specific Barriers to Adherence and Persistence, Patient Counseling, and AE Management for HER2-Targeted Therapy

 

Now I am going to bring back Kristi to talk with me about some symptom management for a TKI. We have a 55-year-old woman who is diagnosed with locally advanced right hormone-positive, HER2-positive breast cancer. She completed neoadjuvant chemotherapy, including her HER2-directed therapy. She had residual disease at the time of surgery and went on to complete a full year of HER2-directed therapy.

 

After surgery and radiation, however, she started her letrozole daily. After completing her HER2-directed infusion, she was started on adjuvant neratinib 240 mg daily to complete 1 full year of treatment. She informs you that she has concerns about starting because she has diarrhea and continues to have irregular bowels since chemotherapy.

 

Kristi, what options would you discuss with her to mitigate bothersome diarrhea and what additional supportive interventions would you recommend?

 

Kristi Orbaugh: My husband probably just wishes I would mute myself probably. When I use neratinib, I have had occasion in patients where I will actually start at a lower dose and then escalate up. She is definitely someone that I would get on Imodium on a regular basis before she ever took the first 1 or Lomotil or colestipol. I have also in this sort of situation had some really good results with bulk forming agents in patients when I am starting them out and starting to escalate that dose.

 

Kimberly Podsada: Yeah, I have found again that once someone finds what works best for them they just stick with it. Again, I have a lot of patients who will find they need 1 Imodium maybe twice a day, and that is what they take and they continue to have a normal bowel movement every day. Again, it is just finding what works best for that patient.

 

Thank you for the comments. I am going to move on to our next section. Please feel free to use the question and answer chat box.

 

[01:15:57]

 

PI3K, AKT, & mTOR Inhibitors

 

Okay. I am going to talk about our PI3 kinase, AKT and mTOR inhibitors.

 

[01:16:07]

 

Approved PI3K/AKT/mTOR Inhibitors for HR+ MBC

 

Currently, we have approval for several therapies, which is very exciting. Everolimus was the first to market, and it is considered an mTOR inhibitor. You do not need a test that shows that you have 1 of these mutations. Everolimus is taken 10 mg orally once daily. These are for hormone-positive breast cancer patients. They are also going to continue on their endocrine therapy.

 

Alpelisib, you need to have a confirmed test of a PIK3CA mutation. It is taken 300 mg orally once daily with food as well as your endocrine therapy.

 

Capivasertib is also approved. Interestingly, it is the first 1 that has been approved for an AKT1 mutation. You definitely want to have your test that shows there is a mutation within the PIK3CA, AKT1 or PTEN. It is 400 mg. It is 2 tablets taken twice a day with or without food. It is an interesting schedule. It is 4 days on, followed by 3 days off. They found that this did help with tolerability.

 

Then we have inavolisib. It is 9-mg orally once a day with or without food. Again, this is specific for patients with a PIK3CA mutation.

 

[01:17:47]

 

Combining Targeted and Antiestrogen Therapies to Overcome Resistance in HR+ Advanced Breast Cancer

 

Although this is busy, this is such an informative slide. I would not spend all day going through this because it is a lot. But it really gives you that good overview of where a lot of the therapies we have discussed, how they interact. We have the extracellular activity and then we have our intercellular activity. We have those extracellular triggers that then create this cascade pathway where we see our PI3 kinase, AKT, mTOR pathway then activated, and where we have our inhibitors that targeted.

 

When we are looking at a lot of these, we want to have additional therapies now that we can offer patients to target these areas where we really find a lot of endocrine resistance is developing. Now we have these more targeted therapies to overcome that resistance.

 

[01:18:49]

 

Indications for PI3K/AKT/mTOR Inhibitors

 

Now the majority of these therapies are approved in postmenopausal women or if they are pre or perimenopausal, then they are going to go on to ovarian suppression. You need a testing that confirms that you do have a mutation. For alpelisib and inavolisib, it is that PIK3CA mutation. For capivasertib, you can have a PIK3CA mutation, but it also is an AKT1 or a PTEN alteration that you may also use capivasertib in.

 

[01:19:27]

 

Key AEs With PI3K/AKT/mTOR Inhibitors: Monitoring and Prevention to Maximize Adherence

 

Here you can see that all 3 of these TKIs will have diarrhea to some degree, stomatitis and hyperglycemia. The hyperglycemia I think has been probably the steepest learning curve for a lot of people. We have gotten a little more comfortable with it if you have used alpelisib since that came to market a few years ago. But it is definitely something we have to pay close attention to.

 

You are not giving someone diabetes, but it is hyperglycemia. We do use medications often that we treat diabetes with. You really need to follow closely the fasting glucose, the hemoglobin A1C, and then you want to optimize the blood glucose before starting treatment. If they have preexisting conditions and they are a pre-diabetic, you pretty much want to get the endocrinologist involved and start them on something before starting 1 of these medications.

 

You will be checking labs sometimes twice a week for 4 weeks, or you may do every week times 2, and then every 2 weeks. Because this is so prevalent, a lot of the providers that I even work with will go above and beyond with blood work because they really want to capture this early on to get the best dose and the safest dose for the patient.

 

[01:21:00]

 

Skill Building and Feedback IV (ARS/Case Discussions): Class-Specific Barriers to Adherence and Persistence, Patient Counseling, and AE Management for PI3K Inhibitors

 

Okay, now we are going to spend some time looking at this patient. Kristi is going to be welcomed back to talk with us about this 68-year-old woman who was diagnosed with de novo hormone-positive, HER2-negative metastatic breast cancer. She completed her first-line of therapy with ribociclib and an AI.

 

At the time of disease progression, she had a ctDNA test that revealed a PIK3CA mutation, and she was started on alpelisib 300 mg daily with fulvestrant. Her baseline characteristics include an elevated blood serum glucose, hemoglobin A1C is 6, BMI is greater than 30. She has intermittent elevated LFTs while she was on her CDK4/6 inhibitor in AI and neutropenia.

 

What would you do to reduce her risk of worsening hyperglycemia? What symptoms would you ask her report to the care team? Are there other symptom risk reduction strategies you would advise? Again, please feel free to use your question and answer box.

 

Kristi, what do you think?

 

Kristi Orbaugh: Well, I will tell you, this is someone that obviously is already comes to us with hyperglycemia. She has got various risk factors that put her at higher risk. I would phone a friend. We are very blessed at the area I work in. We have a wonderful endocrinologist that actually works in our clinic on every Monday. If you do not have an endocrinologist, I realize sometimes those are like finding a unicorn. Sometimes they are difficult to find. But also reach out to her PCP if they have previously been managing this hyperglycemia.

 

This would be a challenge with this patient I would think. Not one that we cannot overcome, but certainly one that is going to take a very aggressive healthcare team.

 

Kimberly Podsada: Right. I think a lot of the providers that I work with are also very comfortable managing metformin now. This is someone who I would consider upfront ordering metformin for and then having her see 1 of our registered dieticians as well. Think about ways to help her improve these numbers through her nutrition as well as through medication. An endocrinologist would also be great, hoping she already has someone.

 

Okay. Anything else you want to add to that?

 

Kristi Orbaugh: No. I think we talked about the appropriate signs and symptoms to report to the healthcare team. Clearly, increased thirst, increased urination, lightheadedness, dizziness, all of those things, we would have covered with her.

 

Kimberly Podsada: One of the things that I also really talk with patients about are expectations. I will let them know that this is a potential, it is highly likely, especially given her situation, and really just encourage her to work with us for the first few months, maybe only a couple of months. But once you find the right dose and the right interventions and medications, this can be very tolerable. You can make this happen.

 

Again, I think just those realistic expectations would also help. Yes, and the glucometer. Our office is also now prescribing glucometers so that they can have easy access at home for checking their blood sugars. When we talk about access to care what can we make sure patients have at home, so they are not coming in so frequently, maybe for those blood draws or they can check it at home. Then let us know what their numbers are. Yes, thank you for mentioning that and putting that in the chat box.

 

Kristi Orbaugh: Again, doing everything we can to set that patient up for success.

 

Kimberly Podsada: Yes.

 

Kristi Orbaugh: We have both had, as I am sure many of the folks on the program tonight have had patients walk in just with those very similar characteristics. We have had to start them on 1 of the drugs that can increase or can cause hyperglycemia and you can work through that.

 

Kimberly Podsada: Okay, so someone is asking, was it easy for insurance to approve the glucometer? I have not run into any issues getting that approved.

 

Kristi Orbaugh: Now I will be honest, that is not something we have done yet at our clinic. I am going to take that pearl back.

 

Kimberly Podsada: Okay. I am going to move on. Thank you for your messages.

 

[01:26:32]

 

Now, let us go back to some of our questions

 

Okay. Now let us go back to some of our questions.

 

[01:26:39]

 

Posttest 1

 

Here is our post-test questions that you started at the beginning. Which of the following strategies would be most effective in helping your patient improve adherence to her prescribed therapy?

 

1. Provide additional education on the importance of adherence;
2. Recommend she join a support group;
3. Use reminder systems and adherence monitoring tools;
4. Educate her on the risks of non-adherence.

 

Please go ahead and take some time to vote here. Kristi and I will discuss the rationale for the correct answer. Let us give you a couple more seconds, otherwise let us close the poll.

 

Okay. Excellent. So utilize reminder systems and adherence monitoring tools.

 

[01:27:41]

 

Posttest 1: Rationale

 

Kristi Orbaugh: Now I do not want to throw a wrench in this, but I do think C is the best answer, but I also think in certain situations each of the answers could be beneficial to certain patients.

 

Kimberly Podsada: Absolutely. That is the answer. What we are saying is there is no single intervention strategy that is going to be effective to approve adherence across all patients conditions and settings. We do need to find what is going to work best for that patient and what that patient's needs are.

 

Okay. Next question.

 

[01:28:23]

 

Posttest 2

 

Which of the following adverse events commonly associated with the addition of capivasertib to endocrine therapy would be important to discuss with your patient with hormone receptor-positive metastatic breast cancer who is considering new treatment alternatives?

 

1. Diarrhea;
2. Interstitial lung disease;
3. Keratopathy;
4. Peripheral neuropathy.

 

Go ahead and choose your answer. What do we need to educate her about starting capivasertib?

 

[01:29:00]

 

Posttest 2: Rationale

 

I am supposed to wait till you answer, sorry. Okay, let us end the fall. Okay. Diarrhea. Yes. Answer A is correct. Diarrhea was the most reported AE on the CAPItello-291 clinical trial. 77% of patients reported diarrhea all grades, and 12% grade 3 and 4.

 

[01:29:33]

 

Posttest 3: Rationale

 

Okay, number 3. When counseling a patient with estrogen receptor-positive/HER2-negative breast cancer with ESR1 mutation before receiving elacestrant, which initial strategy would you recommend to mitigate nausea and improve adherence to therapy?

 

1. Take elacestrant on an empty stomach;
2. Take elacestrant with food;
3. Schedule an antiemetic 30 minutes before each dose;
4. Initiate therapy at low dose and then ramp up to full dose.

 

Kristi did a good job of answering this during her presentation. Please choose your answer and let us close the poll. Okay. We have, take with food and schedule an antiemetic. Take it away, Kristi.

 

[01:30:37]

 

Posttest 3: Rationale

 

What you want to do is have the patient take it with food. Elacestrant. The nausea that I have seen, and really the nausea that is reported is really minimal. Usually, if they just take it with food, that is all they need. I have not had to use an antiemetic yet with this drug. Does not mean that I would not.

 

I also did want to point out for time's sake, we could not really go through the ongoing studies. As of right now this is the only 1 that is on the market, the only oral SERD, but 2 others are in phase III studies. We may see more oral SERDs in the future. In fact, I am sure we will.

 

Kimberly Podsada: Yeah, I agree. Also same here. I cannot even recall needing to prescribe an antiemetic as long as they take it with food.

 

Kristi Orbaugh: But if you had someone that consistently had nausea, taking an antiemetic 30 minutes before is a great answer.

 

Kimberly Podsada: Absolutely agree. Okay, and our final question.

 

[01:31:56]

 

Posttest 4

 

Your patient with triple negative breast cancer and a germline BRCA1 pathogenic variant will be initiating adjuvant olaparib. Given the potential toxicity, which of the following supportive medications should your patient have available?

 

1. Cetirizine;
2. Ondansetron;
3. Metformin; or
4. Prednisone.

 

Go ahead and take a few seconds to answer that. I think we can close that poll.

 

[01:32:45]

 

Posttest 4: Rationale

 

Ondansetron. Awesome. B is correct. Most common reported GI AE in the olaparib clinical trials, so administer antiemetic 30 to 60 minutes before PARP inhibitor. It really helps to manage that nausea, and it was also very transient on the OlympiAD clinical trial and could resolve within 2 days to 5 weeks. Sometimes just getting someone through that initial 5 weeks I have seen the nausea significantly decrease. How about you, Kristi?

 

Kristi Orbaugh: Yeah, I was just going to say the same thing. I would say after you get through those first couple of months, I feel like I have really seen the nausea decrease over that time period. In fact, I have had some folks that do not even need antiemetics after that point.

 

Kimberly Podsada: Right, exactly.

 

Kristi Orbaugh: You have seen that as well. Okay.

 

Kimberly Podsada: I am going to invite Kendall back to wrap us up or take any last minute questions if you want to use the Q&A. I do not know how we are doing on time, so I will let Kendall let us know.

 

Kendall Schick: Perfect. Thank you so much, Kimberly. I just want to thank both of you once again for such a wonderful presentation. It was a great talk and it was a great pleasure to have you both online. Just some finishing polls here.

 

[01:34:24]

 

Poll 3

 

Poll number 3. Do you plan to make any changes in your clinical practice based on what you learned in today's program? The answers are:

 

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

 

Please answer in the dialogue box. We can go ahead and close the poll.

 

[01:34:52]

 

Poll 4

 

Poll question 4. Please take a moment to enter 1 key change that you plan to make in your clinical practice based on the education today. You can enter your response once again in the dialogue box in front of you.

 

Maybe we will just leave that poll open for a little bit while we move on to the next question here or the next slide.

 

[01:35:22]

 

Thank You For Attending

 

We just want to thank you all for attending today and do not forget to claim your credit by going on to clinicaloptions.com. Once again, we just want to thank you all for coming and you can go online for more of the breast cancer coverage. Want to thank you once again to our speakers and our speakers once again. We will stick around for a few minutes here. We have a few minutes left. They can stick around and answer any extra burning questions in the Q&A chat. Otherwise you are free to go. Thank you so much.

 

[01:36:11]

 

Q&A

 

Looks like we have, we have 1 question in the Q&A chat right now. How much time is the ideal time to evaluate adherence and what is the best tool?

 

Kristi Orbaugh: I will start and then Kimberly, please jump in. I really think evaluating adherence is an every time you see the patient occurrence. Just in your own life, think about the last time you saw your primary care provider or whichever doctor you might see regularly. Do you remember every single thing they said, no, or I hope you do not. I hope it is not just me that cannot remember all of that.

 

I think reiterating each time we see them and evaluating how they are adhering to the particular protocol that we have them on, there are tools out there to use. I usually just quiz the patient. I think in oncology we see the same patients over and over and over again and we build those really strong bonds and relationships.

 

The tool I use is just the tool of knowing and caring and loving my patients. That helps me evaluate their adherence, keeping those lines of communication open so they feel okay to tell me. I had a patient tell me the other day, she happens to be on an AI and she does have some arthralgia and myalgias with it. She was going on vacation and she told me that she stopped her medication for the week before and the entire time she was on vacation because she did not want to have those. So keeping those lines of communication open I think is really important.

 

Kimberly, what do you say?

 

Kimberly Podsada: Yeah, I think that while they are still getting familiar with the routine everything is new and scary. For any of my patients that I am starting on a new therapy, I tend to set a reminder to myself in Epic. I start calling my patient just checking in, it has been 2 weeks, how are you doing? Are you taking your medication? Any issues with skipping meds?

 

I do a lot of handholding upfront because this is the time where I feel they are most fearful and stressed. Once they get into the routine, then it is a routine. Then they have learned this new process so that, that seems to work. Then of course, every time I see the patient, I am constantly asking, what are your obstacles? Any issues come up with taking medications, symptom management.

 

I tend to do a lot upfront because I find that that helps me in the long run where there is not as much back and forth with messages and symptom management if we have addressed all of those things early on.

 

Kendall Schick: Well, thank you so much for all of that insight, both of you. We have reached the bottom of the hour, and so we will conclude our broadcast at this time. Thank you so much and have a wonderful rest of your week.

 

Kimberly Podsada: Thank you.

 

Kristi Orbaugh: Thank you.

 

Kimberly Podsada: Thanks everyone for participating.

 

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