AMCP Podcast Series - Listen Up: Breast Cancer Breakthroughs CE Podcast #1 - Danielle Roman

Fred Goldstein  00:01 

Hello and welcome to the AMCP Podcast Series - Listen Up. As we take a deep dive into the challenges, trends and opportunities in managed care pharmacy, follow the show's social hashtag #AMCPListenUP. And to learn more about AMCP visit amcp.org. I'm your host Fred Goldstein. On this episode, we will be presenting a continuing education program on innovations in women's health with a focus on breast cancer. All medications mentioned in this episode are for educational purposes only. This activity is supported by an independent medical education grant from Novartis Pharmaceuticals Corporation, and Merck Sharp and Dohme. AMCP is accredited by the Accreditation Council for Pharmacy Education as a provider of Continuing Pharmacy Education. Instructions for claiming credit are located in the show notes. Please refer to the handout in the show notes for detailed instructions on how to claim CPE credit. At the completion of this activity, participants should be able to discuss the latest advancements in breast cancer management, including pharmacologic and non pharmacologic treatment options to identify the potential benefits, limitations and relevance for different patient populations. It is now my pleasure to introduce our faculty for today's program. Dr. Danielle Roman. She is the manager of clinical pharmacy services at Allegheny Health Network Cancer Institute. Welcome, Dr. Roman.  

Danielle Roman  01:27 

Hi, Fred. Thanks for having me. 

Fred Goldstein  01:28 

It's really a pleasure to get you on. Let's start with the non pharmacologic breast cancer update. The US Preventive Services Task Force recently updated their breast cancer screening guidance, can you provide a summary of the updates? 

Danielle Roman  01:41 

Yes, so that the US Preventive Services Task Force just updated their guidance statement in April of 2024. So just a recent update. And this was notable because they have their screening now is every other year, starting for patients at the age of 40. So we know that there's a number of different breast cancer screening guidelines in existence. I mean, previously, the guidance from this organization was to start at age 50. So they had made this update actually to start a decade earlier at women at the age of 40. And this was really, they said, based on seeing a really high, you are seeing a higher risk of breast cancer in a younger population in more recent years, the really aiming to identify those breast cancer cases earlier for women in their in their 40s. There is I will say different guidance that exists for women that are at high risk for breast cancer, whether that's a personal history, maybe women that have genetic high risk factors. So they would follow different guidance. But for women that are at a kind of a regular or you know, non high risk, it would be every other year, age 40 to 74. So I think that that's a that's a pretty big change. Just to note that this is one of the guidance guidance in existence. We have a couple of other guidance documents. One of those that's frequently cited is the American Cancer Society's breast cancer screening guidance that does differ. That guideline has it is optional for women between the ages of 40 to 44. And then once women are at the age of 45, the recommendation is annual screening. So different from what we just talked about an annual versus every other year.  

Fred Goldstein  03:30 

Got it? And you sort of touched a little bit on why the guidance changed. Are there any other reasons? And how do you think that's going to impact care? 

Danielle Roman  03:38 

Yes, I think that, you know, the reasons cited by the US Preventative Services Task Force really, really was seeing an increase in the incidence for younger women. So they cite that rates are increasing by about 2% each year for women in their 40s. So with that notable change, wanting to change that to an earlier screening to hopefully see potential benefit in in that younger age group, as well as they identified some modeling that looked at new screening, and the new data on screening in the US and outcomes specific to black women, and seeing a benefit of starting earlier screening. So I think that, you know, this has the potential to hopefully save more lives with earlier screening, but it does certainly present some challenges and actually making this happen for women. So making sure that there this is part of education on all levels of healthcare, so primary care physicians, those of us in oncology and in other disciplines to make sure that we're encouraging screening for women starting in their 40s. Either every year as the American Cancer Society recommends or every other year based on the US Preventative task Services Task Force recommendation. 

Fred Goldstein  04:55 

Got it? I know there have been many recent advances in the pharmacologic treatment of breast cancer specifically metastatic disease. Can you provide a brief overview of the current treatment options?  

Danielle Roman  05:05 

Yeah, so there, this is a this is a big question because there is a lot here. But I think as a high level overview, definitely seeing a lot of updates across the board in breast cancer and particularly in the metastatic setting, there have been, you know, a lot of recent additions to guidelines or options for our patients. So when we look at the metastatic treatment setting, we know we have, we're primarily relying on systemic therapies at this point. So systemic pharmacologic therapies. Generally, for patients, we are not looking to local strategies like surgery or radiation to the point where the cancer is spread. So our options here is that as a high level overview, may involve chemotherapy for certain patients, endocrine therapy for those patients that are hormone receptor positive. Potential for targeted therapies, and that's a pretty big category there. But we could be talking about things like HER2  targeted agents for patients that have HER2  positive or HER2  low disease. We have additions of oral targeted therapies now, particularly in patients that have hormone receptor positive HER2 negative breast cancer. So that is the most common subtype that we see it's we have a lot more options here with oral therapies. There are CDK4/6  inhibitor class or added option for an Oral SERD agents that target the PI3K pathway. Then we also have antibody drug conjugates as options for patients usually in a more refractory line of therapy, as well as immunotherapy. But I would say here in breast cancer immunotherapy really is a very specific indication in those patients that are triple negative, meaning they don't express estrogen receptor, progesterone receptor or HER2. 

Fred Goldstein  06:54 

Dr. Roman, you mentioned incorporation of oral targeted therapies. Can you elaborate on those options? 

Danielle Roman  06:58 

Yeah, so we have seen a huge growth in the setting of oral agents, which is great, I think, from a patient standpoint of the convenience of having oral therapies, that we've had a lot of growth, particularly in that what I mentioned was the most common subtype of breast cancer, the hormone receptor positive HER2 negative patient population. So I think really, the first one I'll start off with is the CDK4/6 inhibitor class. So we've had these for a number of years now. But we continue to learn more about them and kind of the best use of these agents in metastatic breast cancer. And I'll just say even a little bit in early stage breast cancer as well. So this class, we have palbociclib, ribociclib, and abemaciclib. So the three drugs within that CDK4/6 inhibitor class. And as a whole, across the board, in all trials, we've seen improvements in progression free survival. So really dramatic improvements in both the frontline metastatic disease as well in patients that are in second line or beyond. So in some of these cases, that you know, a doubling of progression free survival, so really, you know, an exciting advancement. And in some cases, we've also seen an overall survival benefit in some of these trials. So not all of them. I mean, it's definitely kind of created some controversy within the breast cancer field of whether there's a preferred agent here or not. But definitely, you know, these agents have revolutionized the treatment for hormone receptor positive HER2  negative metastatic breast cancer. And just a little bit of of mention out of the recent ASCO 2024. meeting, there was some data coming in from the post Monarch trial. So this was long awaited data at looking at patients that receive a CDK4/6 inhibitor and endocrine therapy in the frontline setting. We have such great benefit there is is there any benefit of continuing with the CDK4/6 inhibitor after progression? So kind of the was an unanswered question for for many years, we had some small trials that had shown differing outcomes. So we're seeing in post Monarch, that there does appear to be some benefit of switching that CDK4/6 inhibitor and switching the endocrine backbone at the time of progression. But I would say it's a modest benefit. So I think for patients that have other options with targeted therapies, we probably would be leaning on that. But we do have this option for some patients that may not have other targeted therapy options. So some some new exciting data there. So that was kind of looking at that CDK4/6 inhibitor class. And I'll just add a little bit with other targeted therapy options that we're we're now seeing used in metastatic breast cancer and again, this is really predominantly in that hormone receptor positive HER2 negative patient population. And that's the the PI3K inhibitor class. So we have a apelasib, we now have a newer edition capivasertib. And then we have everolimus we've had for some time now. So I think that you know, some exciting data here and this is for apelasib and capivasertib these are particularly for patients that exhibit alterations of that PI3K pathway. So for apelasib, we have options for patients with the PIK3CA mutation. And for capivasertib, we see a little bit more of an expanded indication here. So other targets within this PI3K pathway. So not only that PIK3CA mutation, but also patients that have an AKT or a PTEN alteration. So potentially being able to have some expanded use. And then now just throw in that we have everolimus that we've had for many years that is not for a specific target can be used across the board for all patients even without those mutations or alterations. So a number of options, targeting that pathway. And that is just in the second line setting or beyond. So patients with progression paths first line treatment. And the last option I'd like to mention with that oral targeted therapy is elacestrant. So that is a selective estrogen receptor degrader. So we've had Orserdu on the market for many years with fulvestrant, which is an intramuscular injection, we now have the addition of elacestrant, which is an oral agent with that same mechanism of action, and is approved for patients that have an ESR1 mutation. So this is a mutation that generally is acquired over time that patients are on endocrine therapy. So with the AI class, the Aromatase inhibitor class, they can acquire mutations that make them resistant to the AIs, and this is one of those mutations that's frequently seen. And so now we have a target for that with elacestrant. And then just like to point out that this is something because it's an acquired mutation, it should be tested at the time of progression on endocrine therapy, and it's recommended to test that with a liquid biopsy. , 

Fred Goldstein  07:25 

Thanks Dr. Roman. And one of the other areas that a lot of people discusses minority populations are often underrepresented in clinical trials? Do we have any information about the use of these agents in minority populations? 

Danielle Roman  12:18 

So unfortunately, we have very little here to guide us. The majority of the patient populations we've seen in a lot of these clinical trials has been a Caucasian population. So we have often in practice needed to extrapolate that data to other patient populations. Will say that there is a little bit of data and this was post hoc analysis that was done with one of the CDK4/6 inhibitors or palbociclib, an endocrine therapy. And they looked at the efficacy and safety of this combination in black and Hispanic patients that were enrolled in the PALOMA trial. So kind of looking across the board at the PALOMA trial, so PALOMA-2 and PALOMA-3. And what they found was similar outcomes between the black and Hispanic populations as to what was seen in that intent to treat population. So kind of giving us some competence in what we're doing in practice, which is really an extrapolation of that. So unfortunately, it is, you know, an area of practice that we sorely need more information and greater representation of those populations in clinical trials. Generally, they're less than 10% of the populations that we see in some of these larger trials. So we do have some data, a lot of extrapolation that's happening, and hopefully, we'll have some better data in the future. 

Fred Goldstein  13:44 

Right, can you give us some insights on new developments in breast cancer treatment, and what might we see added to guidelines in the future? 

Danielle Roman  13:52 

There's a lot of exciting information that was coming out of the ASCO 2024 Meeting related to breast cancer. I think some of the most exciting things that we saw one of the trials presented was the DESTINY-Breast06 trial. So this was a just very briefly, this was a trial of patients with hormone receptor positive metastatic breast cancer. And these were patients that had either HER2 low disease, so not patients that were historically considered to be HER2 positive but had some expression of HER2 on the surface of cells. And then they also included patients that were considered HER2 ultra low. So not even meeting that definition of HER2 low but had some amount of staining. So somewhere between what we say is an IHC or immunohistochemistry of zero and one plus so very little staining but something that existed with HER2 proteins on the surface of cells, and they consider that population to be called Ultra Low and they showed benefit of giving the antibody drug conjugate trastuzumab deruxtecan to these patients. So, you know, a significant benefit here that we saw in progression free survival. So I think that some of this data really could be could lead to the expansion of trastuzumab deruxtecan to, potentially to patients with HER2  ultra low disease in addition to that HER2  low population where we're already using it. And I think that we could also this potentially could expand the use of trastuzumab deruxtecan into earlier lines of therapy. So in this particular trial, they did it after patients had progressed on their endocrine therapy, but before chemotherapy, so you know, this trial really could move trastuzumab deruxtecan up in lines of therapy. So I think that was a really influential abstract that was presented. But definitely some challenges here in particularly in identifying these patients with HER2 ultra low disease. That is not something that has been historically reported out, been reported out by our pathology colleagues. So I think, you know, challenges and making sure that we're appropriately identifying these patients that could benefit from trastuzumab deruxtecan. So that was a big one. And then I think the other one that was is worth a mention is the INAVO120 trial. So this was looking at a novel investigational PI3K inhibitor. So I had mentioned a couple of PI3K inhibitors that we were using in practice. So this is one that is not yet approved. And then they were looking at it in an in a novel setting as well. So this would be giving that PI3K inhibitor in combination with CDK4/6 inhibitor and endocrine therapy in the frontline setting, to moving it up from treating more PI3K inhibitors in the refractory setting to giving it upfront, and giving it as a triplet, so two targeted therapies in combination with endocrine therapy in patients with a PIK3CA mutation. So I think, you know, this could be, you know, an exciting change to guidelines for those patients that have the PIK3CA mutation. But certainly, you know, some challenges there. And I will just mention that the trial did use palbociclib as the CDK4/6 inhibitor of choice, it may it's often not the one we're reaching for frontline and practice these days. But that was what was used in this trial. So I think in the future, if we do have an approval of this drug in the setting, we would we probably be going for using a little bit more palbociclib than we have been currently. 

Fred Goldstein  17:35 

Well, Dr. Roman, I'd like to thank you for sharing your expertise with us. 

Danielle Roman  17:38 

Thanks for having me. 

Fred Goldstein  17:39 

To learn more about this topic, check out an on demand webcast featuring Dr. Danielle Roman and Dr. Susan Wojcicki, available on AMCP learn.org. To claim credit for today's podcast, you can go to AMCPlearn.org/code and enter the code V is in Victor. A is an alpha B as in Bravo, S as in Sierra, E is an echo. W as in whiskey. That's VABSEW. From there, you will need to go back and complete the evaluation to claim your CE. Full instructions are available in the show notes. And thank you for joining us today. If you like this show, you can find all our episodes at amcp.org/podcast on our show page at HealthcareNOWRadio.com or on your favorite listening platform by searching Healthcare NOW Radio. You can follow our shows social hashtag at #AMCPListenUp. Don't forget to share, like and follow AMCPorg on LinkedIn, Twitter, Instagram and Facebook. I'm Fred Goldstein for AMCP. Until next time,