Value-based Considerations of CDK4/6 Inhibitors in the Treatment of Metastatic Breast Cancer - Episode 21
Caroline Block, MD discusses the outcome of implementing clinical pathways and the future use of pathways.
Caroline Block, MD: For the way we construct our Clinical Pathways, we focus on what the specific situation is. From the beginning, is this adjuvant treatment, or is it DCIS [ductal carcinoma in situ]? I should start with that. Is it adjuvant for basic cancer? It is locally recurrent cancer? Is it metastatic cancer? We’ve already got several different branches, and we now have the inflammatory breast cancer branch as well. Within each of these, it’s broken up by not only subtype but stage. We will mention the toxicity of certain treatments, where a treatment can be adapted based on patient’s age, preference, or preexisting toxicity.
In the metastatic pathway, which is obviously an important part of the pathway, our focus is primarily on, for the non-HER2 [human epidermal growth factor receptor 2]–positive patients, single-agent treatments with reasonable efficacy, but also with quality of life. In general, we don’t do combination treatments, except for situations of visceral crisis where a rapid response is needed, and those actually happen a lot less in reality than you would think.
It is patient centered in the sense that we give options based on a patient’s preference and preexisting toxicities, and the focus all along is on what’s efficacious with lower toxicity, particularly in the metastatic setting. We also divide it up in the metastatic setting by line of therapy, so it’s not just 1 big, long list of all the things you can use. In triple-negative breast cancer, we’ll list first-line treatment, second-line treatment, and third-line treatment. Sometimes, we list just third line and beyond, and sometimes there’s a fourth line and beyond. When we get to those later lines of therapy, we also list the reasons someone might want to stop treatment and go to supportive care because even though in breast cancer we have a long list of treatments we can use based on a patient’s toxicities and performance status, there are situations where it may be time to stop treatment and focus on palliative care instead. That’s definitely built into our clinical pathways as well.
When we develop clinical pathways, and we’re looking at new trials or new drugs that have been approved, there’s always focus on the patient population that was used. What was the line of therapy? Was it first, second, or third line? We pay close attention to that. Did it include patients with active brain metastases? Did it not? Were these patients mutation carriers, such as BRCA1, BRCA2 carriers? All that is closely looked at. We discuss this, and we will put those guidelines into our clinical pathways. This is recommended in patients with active brain metastases or if patients have a BRCA mutation, and this is a specific treatment they should get. That’s the detailed part of the discussion.
We’re lucky. When we discuss these drugs, not always but often among our group, they’re closely involved in clinical research, so we often have someone in our group who was either involved in that study or a similar study and had deep knowledge about a particular HER2 drug, a particular triple-negative drug, or CDK4/6 inhibitors or PARP inhibitors, and they’re able to give us some additional depth of knowledge about what group this makes sense in and what things we need to highlight when we have this in our clinical pathways.
At Dana-Farber, the outcome we’ve seen using clinical pathways is that we are able to see as a group what we’re doing and when. If we are using a lot of capecitabine first line, and we had not previously stated we should do that, we go back, look at it, and discuss if it makes sense to change our clinical pathways or if we should change what we’re choosing in a given setting. We’re certainly doing what we recommend. If we recommend a given treatment, we’re following in that situation. And if not, why not?
It also helps since, like many academic centers, we [at the Dana-Farber Cancer Institute] have a main academic campus, but we have several satellites as well. At our satellites, the oncologists may be more general oncologists. They may have some expertise in breast cancer, for instance, but they might also be treating a variety of different cancers. We’ve seen the advantage of that: At the center where those of who treat only breast cancer put our heads together and figure out the nitty gritty of what we want to do in a given situation, our satellites have easy access to that and can look in and see what are they doing at our main campus and make sure they’re in line. For our satellite systems, it’s helpful.
Medicine changes so quickly. When I first started, which was awhile ago, it was easy to keep up with the different treatments for the different cancers because there weren’t that many treatments, and it wasn’t very molecular at all. Now there are so many layers of information and things we have to think of that it’s helpful to have that in a guideline, like the clinical pathways, and know that this is a real-life document. This is not just something someone imagined. This is what we’re doing day to day, what we feel works and what we feel is best and in the patient’s interest.
That’s been 1 advantage. Everything is thought through, and we’re doing things uniformly. We’re providing that information to places where they may not treat just 1 particular cancer type.
Another advantage is that, as we’re planning clinical trials, we can look and see how many patients we have in that situation for which a trial would be helpful. We can look at how many patients started second-line treatment for metastatic HER2-positive breast cancer or how many patients with previous first-line CDK4/6 inhibitors went on to receive a second-line CDK4/6 inhibitor or another agent. They can look at that space and say, “We started 16 new patients in the last month. That’s a situation for which we definitely have a need for a new trial.” Or we can say, “We started only 3 new patients in the last 3 months. We’re not going to have enough numbers to support a trial.” It’s been helpful at designing trials as well.
As far as how clinical pathways will develop over time, there is potential for a lot more things we can do with it. One is, as I mentioned before, fine-tuning more of the toxicities, especially in the metastatic setting, by being able to prioritize what toxicities are most important in that given situation to avoid and having it help you rank the prioritized treatments based on that.
Another thing I see us doing is using it more for specific situations. We recently designed, implemented, discussed, and put together a clinical pathway for inflammatory breast cancer because there are differences in how that’s treated versus other types of breast cancer. That took a lot of work and a lot of discussion, but people felt good at the end that we had come together with that.
The next thing we’re looking at designing is a specific pathway for breast cancer with brain metastases. We’re lucky to have an active group of medical oncologists, neurosurgeons, neuro-oncologists, and radiation oncologists. That group works closely together to see a lot of patients who get treated by us, as well as sending for opinions. Using that expertise, we can come up with what you do in those specific situations when you have active brain metastases, how that should change your treatment, and what treatments make more sense than others.
Another situation that we’ll look at doing in the future is this: We have Rachel Freedman in our group, and she has expertise in treating older women with cancer. It will be nice to have that built in. There’s nothing in our current clinical pathways that say to do this for this age and that for that age, other than basing it on menopausal status. It is helpful to know, as people get older and they have other comorbidities and other medical challenges, some ways you would potentially modify the treatment that would make sense in that population. What works? What doesn’t work? What’s too toxic? What’s well tolerated? It would be nice to build that into our clinical pathways so it can be easily accessed there.