Precision Oncology in Breast Cancer and the Role of Managed Care

Welcome to Unscripted, the AMCP podcast, a look inside managed care pharmacy.

Steve: What if we could identify treatment resistance in advanced breast cancer before it appears on a scan? Emerging advances in biomarker testing and circulating tumor DNA monitoring are creating new opportunities to detect disease changes earlier and potentially act sooner But as the science evolves, managed care stakeholders are facing important questions about evidence, coverage, implementation, and how to ensure healthcare infrastructure keeps pace with innovation.

Welcome to Unscripted, the AMCP podcast. I'm Steve Kheloussi, principal consultant with Kheloussi Consulting and a managed care pharmacist by background. In this episode, we're exploring insights from a recently published AMCP Market Insights supplement in the Journal of Managed Care and Specialty Pharmacy, focused on managed care approaches to ESR1-mutated advanced breast cancer.

The publication is based on a multi-stakeholder roundtable that examined the evolving role of biomarker testing, circulating tumor DNA monitoring, and emerging treatment approaches in hormone receptor-positive metastatic breast cancer. We'll discuss what payers should know about the rapidly evolving biomarker testing landscape, the perspective shared by clinicians, patients, and managed care stakeholders, and what an ideal future state might look like as scientific innovation continues to advance.

Joining me today is Dr. Kirollos Hanna, one of the participants in the AMCP Market Insights panel discussion. Kirollos is the director of pharmacy at Minnesota Oncology and an assistant professor of pharmacy at the Mayo Clinic College of Medicine. Welcome, Kirollos. We're happy to have you. 

Kirollos: Thanks for having me, Steve.

Steve: Absolutely. And so I gave the audience a brief introduction, but would you mind telling us a bit more about yourself and the work that you do? 

Kirollos: Absolutely. So as, as director of pharmacy I work as part of a large community oncology practice covering quite a large area in a metropolitan area in the Twin Cities, Minneapolis-Saint Paul.

My role, I oversee everything as it relates to pharmacy services, clinical, operational, as well as economics. I also have an academic role with Mayo Clinic from a, from an education and research perspective. My areas of interest, Steve, are really focused in breast cancer on the solid side and genitourinary cancers, as well as B-cell cancers on the hematologic side.

So it's really exciting to actually spend some time with you today because a lot of these disease states some of the topics that we're gonna cover, like ctDNA testing is starting to have a bigger role in breast cancer. It's even starting to have a role in bladder cancer, right? That's where the genitourinary side is.

And then also, how does this relate to things like MRD testing in the hema- hematology side, right? These are all things that are continuing to evolve and really excited to spend, a little bit of time, you know, digging a little bit deeper into this. 

Steve: Yeah. Thank you so much for that background, and it's clear why they selected you as one of the experts on the panel.

So before we dive into the findings, could you briefly explain what AMCP Market Insights is and what prompted this particular panel discussion around ESR1-mutated advanced breast cancer? 

Kirollos: Certainly, Steve. So when we look at the AMCP Market Insights panel it's really intended to be a forum that brings in multiple stakeholders.

It includes pharmacy personnel practicing medical oncologists, health plans, different type of organizations like integrated delivery systems, community oncology, large academics. It even brings in PBM's prior authorization representatives and patient advocates. One thing that I really appreciated about this particular panel is that we did have a patient advocate as part of the group.

Now, as it relates to the deliverables, really, we're not looking to reach a formal consensus regarding a particular topic, but it's really to evaluate where the science is going, what's important to payers, what's important to health systems, practicing clinicians, as well as the patient, where there may be uncertainties and some of the challenges that we see.

And it's really aimed to find a deliverable or have some deliverables where managed care organizations can, it can help support them making informed coverage decisions in terms of what's important and what's going on. Now, the topic of ESR1 mutation is becoming extremely interesting within the early breast cancer patient population.

We're seeing, you know, testing is very important because what we're learning is as these patients are developing an ESR1 mutation, they ultimately have worse prognosis. So what do we need to do when we discover a patient has an ESR1 mutation? When you look at this particular mutation, it is associated with resistance to hormone therapy and endocrine therapy, right?

So these hormone receptor-positive, HER2-negative advanced breast cancer patients, having that mutation, some of the studies have shown us that maybe switching to a SERD, like from the PADA-1 or the SERENA-6 study, has been shown to improve progression-free survival. So we're trying to see how do we now utilize this in our standard day-to-day practice to potentially tailor therapy based on these, the circulating ctDNA to help us detect ESR1.

In our supplement, we actually referenced that in some of these advanced breast cancer patients, ESR1 mutations could be as prevalent as up to half of the patients, forty-five percent or so. So it's certainly something that is an important topic, not just to the patient, to the clinician, but also to the payer.

How frequently we test? When do we test? Does testing allow informed treatment decisions to change therapy? Do we have enough data there? So really looking forward to that discussion with you today 

Steve: Yeah, that's excellent. You raised a lot of really important points that we want to make sure that we come back to.

And I think one of the important themes that emerged from this supplement was that this idea that innovation is moving faster than many existing healthcare processes, right? And so from your perspective, how does this disease area illustrate the broader challenge of scientific advances that are outpacing not just the regulatory side of things, but also the payments, policy, and operational infrastructure that we're seeing?

Kirollos: Great question, and I think this is a ultimately a textbook example of how innovation is moving faster than the systems responsible for operationalizing things, right? The traditional oncology infrastructure is largely organized around recognizable clinical events, a new diagnosis, radiographic progression, treatment failure, and then starting a new line of therapy, right?

All of the prior authorization criteria, treatment pathways, claim systems, and even quality metrics are anchored around this cookie-cutter approach of one thing leading to the next thing leading to the next thing. Now, when we look at ctDNA monitoring, it introduces a different paradigm in the grand scheme of things.

Patient can remain clinically stable if their, however, their ctDNA could start to indicate signs of resistance mechanisms, right? You don't have a true radiographic progression, but you now are having rising levels of ESR one. That is a hallmark characteristic of drug resistance. So now the science is taking us or having us starting to consider whether this molecular progression, not conventional progression, is something that we need to move on or have a potential intervention, right?

PADA1 was a phase three study. It was specifically designed around this concept. Patients that were receiving an aromatase inhibitor with palbociclib, they were monitored for rising ESR1 mutations. If there was a rising mutation, or there was a newly detected mutation, but patients did not have synchronous disease progression or radiographic progression they were then either randomized to an aromatase inhibitor or switched to fulvestrant while maintaining palbociclib.

What we learned is that there was an improvement to progression-free survival. Now, taking SERENA6, which is also ano- another important study to look at, Steve, this looked at chemizestrant in combination with CDK4/6 inhibitions. These patients received six months of first-line aromatase inhibitor plus CDK4/6 inhibition.

ctDNA was being tested every two to three months. When an ESR1 mutation emerged or we started to see rising levels without a radiographic progression as well, they entered into the randomization phase where they then went on potentially chemizestrant. And what we learned there as well is that these patients are having an improvement in progression-free survival.

We'll get into it a little bit later, but even interestingly in SERENA6, they looked at patient quality of life. And when we start talking about our patient representative, we'll highlight some important things from SERENA6. So here we're seeing the ability, the data showing us that the ability to detect an abnormal mutation, ESR1 Could lead us to switch therapy.

We know it's associated with progression-free survival from two studies. OS is still immature at this point, and that's one of the challenges. But it is not part of that standard oncology strategy that we would generally be following, waiting for true progression. 

Steve: Wow, there's a, a lot to unpack there. So just to make sure, for those who don't work in oncology on a day-to-day basis like myself, I want to make sure that I'm understanding this.

So this idea of circulating tumor DNA fundamentally changes the way that we are approaching oncology management from this idea of waiting for some kind of progression before we change to more proactively monitoring the patient and proactively changing treatment based on those circulating tumor DNA levels.

Kirollos: You're spot on, Steve. Exactly. And, but the main question, and one of the most important questions, right, is having that intervention early on, right? When we start to detect ctDNA showing us rising levels of ESR1, if we switch then versus waiting truly for the patient to have a true clinical progression of their disease, longevity-wise, is the patient living longer?

But it's not just about living longer, right? It's not the only metric that we need to be looking at. Quality of life, the tumor control, subsequent lines of therapies, and various complications that come with it, but definitely thinking about oncology completely differently from what we're learning.

Steve: Yeah, and that requires a systematic change, I would imagine, before we can actually implement, you know, these therapies into practice and coverage for these and all of that. You mentioned a couple of times, quality of life, so I want to go back to this idea that there was actually a patient representative, a patient advocate on this panel, and that brings a unique perspective to this discussion.

So what did you hear from the patient community about what matters most to them when it comes to this topic? 

Kirollos: Thanks, Steve. So, I think the patient and all, and, you know, and all that we do really needs to be the center of this. And the patient perspective was actually extremely insightful, from our panel.

And one thing that really resonated with me was the patient stating that statistically significant outcomes is not automatically the same as the patient valued outcome, right? Patients, of course, want survival. They want to have as much life as we possibly can give them, but they value survival in the context of maintaining function, maintaining independence, the quality of life, and the ability to participate in meaningful life events, and I think that's extremely important.

When we were talking in the panel some of these metrics that we want to see from this whole concept around early ESR testing and potentially switching therapy, does that ultimately translate into a delay in pain progression, time to chemotherapy the degree in you know, in what in how the patient feels and looks sick, right?

So this concept of ESR1 mutation, even if it doesn't translate into an overall survival benefit, there are clinical metrics that align with this particular patient perspective. But we also have to keep in mind, testing for ESR1 from a patient perspective, what does this mean? Scheduling, travel time, time away from work.

Is the testing going to be coupled with a physician appointment or an injection or something they're coming in for, or are they going to be independent appointments that they're coming for testing? The cadence of ESR1 testing is not yet well-established in when and how often to test, so that's another area where it does add a little bit of a burden to the patient.

Not to mention treatment costs, right? Or testing costs, laboratory costs, payer coverage versus potentially out-of-pocket responsibility. That can sometimes be a little bit challenging. And then also when you think about it from the patient perspective Is the result going to be actionable? Why am I testing?

Understanding why am I testing. And if we do discover that I am going to start demonstrating circulating DNA, ctDNA that has ESR1 mutations what does that mean for me? Am I going to be able to go on an alternative therapy versus waiting until that true progression? So all of these things are important.

And I will just highlight that relating it to the data, going back to SERENA-6, right? So the SERENA-6 study strengthened some of this discussion and aligned with some of the things that we got from our patient representative because the trial reported a delay in the deterioration of patient-reported global health status, as well as an improvement in their quality of life.

So that was something that was very nice to see from this whole concept, that it's not, it doesn't just come down to an OS benefit or not. 

Steve: Yeah, so there's some of that patient-centered outcomes data that, that matters so much, but is somewhat discounted by payers sometimes as well, which is a little bit challenging.

You raise a lot of really good points and I want to go back to one in particular, which is this idea that if these patients get this testing and it shows that they need to switch therapy, will that therapy even be covered? And this speaks to the idea of aligning benefits between the medical benefits, between the laboratory benefits, potentially pharmacy benefits, depending which benefit that drug is going to be covered under.

And then the stakeholders themselves have to be aligned as well, right? The payers, the PBMs, specialty pharmacies, providers, all of these individuals have to kind of be thinking the same thing, or at least on the same track. So what are some of the, the practical consequences when that, you know, those systems don't work together properly?

Kirollos: Excellent question. So we keep hearing precision oncology, precision oncology, precision oncology, right? And for precision oncology to work appropriately, the diagnostic and treatment components have to function as a single care pathway. The patient first needs the correct biomarker test, of course, right?

The result must reach the treating team in a usable timeframe. The clinician must connect that result to an evidence-based treatment backed by solid data and guidelines. The payer must also receive the necessary documentation, and the medication must be approved and dispensed with as much as possible unavoidable interruptions in therapy in the process.

Each of these steps, involve different organizations, right? The test is managed by laboratory. The existing CDK4/6 inhibitor, the oral might be dispensed through a specialty pharmacy. The new oral SERD by be- might be managed by a PBM and a different specialty pharmacy. You have the prior authorization team and the prior auth might require proof of the mutation, prior endocrine treatment, duration of treatment, imaging status, evidence of progression, true progression, and these are going to all pose a lot of barriers.

And when they're not aligned, the provider and the HCP team might ultimately have to submit clinical inf- information several times, where I'm submitting testing here, for this prior authorization, then for this prior authorization, and it becomes really difficult. Our panel in our discussion proposed several practical solutions to help alleviate some of these fragmented work streams.

We have common treatment pathways and standardized documentation checklists. If there's opportunity for auto approvals for requests that meet evidence-based guidelines and evidence-based criteria for payers to work with us to help establish these auto approval processes. Longer authorizations are of course going to be warranted where appropriate and maybe more clinically complex scenarios.

But we, you know, for example, my practice has this relationship, gold carding approaches that can be granted for institutions that have demonstrated consistent compliance with the payer policies, right? And just closer coordination between laboratory, medical, and pharmacy benefits. So having some policies and procedures can really help mitigate some of that fragmentation and reduce some of the time gaps that we tend to see.

Steve: Yeah, that's incredible. So I just want to clarify, you actually have gold carding agreements in place right now? 

Kirollos: We do. We do. 

Steve: Wow, okay. 

Kirollos: We actually have three payers where we've worked with them for gold carding. 

Steve: Yeah, that's great. You know, we have talked about gold carding as a way to fix the prior authorization system for many years, but, you know, there are a lot of barriers to implementing that.

And, you know, it's one of those things where payers will sometimes engage in these agreements, find out that it wasn't beneficial for them and back out, and then it's just with that individual provider it didn't work out, but it almost poisons the well in some ways that, you know, really don't see gold carding from that, that payer moving forward because they had one bad experience.

So yeah, excellent to hear that that's working out well. 

Kirollos: And I will say, you know, Steve, it really comes down to good communication with your payer partner and transparency, right? Alignment doesn't have to mean that you're removing utilization management. It simply means it's designed where the management is actual around clinical pathways rather than treating each component as an unrelated transaction, right?

When we do that, that's where we start to see some of the challenges, but it's been very successful. 

Steve: Yeah, that's really great to hear, and I'm sure that has a profound impact on the patient outcomes as well. You raised a number of action items, and I'm all in favor of leaving our audience with, you know, a few take-home points that they can implement tomorrow that, that are gonna be, you know, real world, and have some meaningful implications for their practice, for their patients, for the providers that they work with.

What do you think is maybe the lowest-hanging fruit, something that a payer could potentially institute with very limited overhaul of their existing systems? Like gold carding is, that takes a lot of work to implement. But what's something that they can just reach for to get an immediate win?

Kirollos: Absolutely. So I think really, I mean, as we're advising the payer or looking from a payer lens they need to create a cross-benefit precision oncology framework. I mean, that is really where oncology and cancer care is shifting, whether we're talking ctDNA positivity or ESR1 mutations or we're talking about MRD negativity, right?

ctDNA is now, you know, outside of the breast cancer realm, it's even playing a role in bladder cancer. You know, the, there's guidelines around testing and what it means and what you do. That framework that needs to be developed should include medical oncology, pharmacy, laboratory services, utilization management, analytics teams, and patient support functions.

And really, I think we need to come down and answer a couple of core questions. What is the intended patient population? What is the clinical purpose of testing? What constitutes an actionable result? What documentation is necessary that we can provide? And what outcomes will be measured that are going to be important clinically, important to the patient?

And I think by having that framework, having that, those key stakeholders together, and answering these core pillar questions, I would say, could really help streamline this. And I will also highlight that our supplement recommends Evidence-based treatment pathways, streamlined authorizations, as I mentioned, real-world evidence generation is extremely important, aligned coverage policies, and this multi-stakeholder collaboration, to help, you know, improve this overall ecosystem.

Steve: Yeah, no, and I think this is an excellent first step, and, you know, I'll try to make it even simpler and you let me know if you agree with this. The first step that payers can take tomorrow is look at their benefits and make sure that they align, and if they don't, just schedule a meeting with all of the important people within your company to make sure that we're, you're starting that conversation.

Kirollos: Correct. 

Steve: Is that a reasonable first step? 

Kirollos: Absolutely. And really, you know, to be honest with you, Steve, the payer in the biomarker space, for example, does not need to predict every future biomarker. They just need a repeatable process that can distinguish promising biomarkers from a clinically actionable one, and then be able to update their policies fairly quickly 

Steve: Yeah, I love that.

And the idea of pivoting quickly as new evidence emerges seems like it's gonna be all the more important as we continue in this this, you know, new approach to managing oncology that we maybe haven't considered in the past. So I'm gonna ask one last question as we wrap up here. What, you know, from your perspective, what does the ideal future state look like for precision medicine in breast cancer?

And how can payers, providers, laboratories, manufacturers work together to ensure that advances in that biomarker-driven care ultimately translate into better patient outcomes? 

Kirollos: Excellent question as well. So the ideal future state is not more testing. It's more purposeful testing connected to timely evidence-based action.

We need to be able to discern what outcomes are going to be important for our patients, right? What is going to be important based on some of the things that I've highlighted that are important to patients, pain control, treatment, you know, delay to progression, delay to chemotherapy, et cetera. As organizations and institutions, we need to have treatment pathways that are evidence-centric and evidence-based, where they bring in the best level of data, to account for prior treatment, tumor biology, comorbidities, toxicity, as well as patient preferencing.

From a payer and provider perspective, we really need to partner together to be able to determine, you know, this ever so evolving field, oncology is consistently changing, and working together through a, a multi-stakeholder collaboration is going to be really important, I think, for that ideal future state.

Steve: I love it. Very well said. And that will actually wrap up our time. Kirollos, thank you so much for all of your insights today. This has been fantastic. And thank you so much to our audience for taking the time to listen. We'll see you next time on Unscripted.