Defining Value for the Treatment of Brain Metastases in Metastatic HER2-Positive Breast Cancer - Episode 13

Approaching At-Risk Patients for Brain Mets in HER2+ mBC

A payer and provider perspective on treating all patients with HER2-positive mBC as if they are at risk for brain metastases and the use of clinical pathways to ensure the correct patients are treated.


Kevin M. Kalinsky, MD, MS: We always get concerned about patients who have metastatic disease. Could they or could they not have brain metastases? I mentioned earlier that, for patients who are newly diagnosed, the guidelines don’t suggest checking for brain metastases in the absence of metastases. That could change, and part of the reason is that our drugs are better in terms of getting to the CNS [central nervous system].

It’s 1 of the things patients are concerned about. When do they have brain metastases? If not, is that something that’s going to develop for them? Now that we have active agents in the CNS, such as tucatinib, lapatinib, and neratinib, with what we discussed about the potential for some of these other larger molecules, it’s possible that there may be a benefit for screening earlier, including the fact that we see overall survival benefits for something like lapatinib. That paradigm could shift over time as we have better therapies.

Sarah Sammons, MD: Would I treat all patients with HER2 [human epidermal growth factor receptor 2]–positive breast cancer as if they’re at risk for developing brain metastases? The answer to that is yes because we know that half of patients will ultimately develop HER2-positive brain metastases. The holy grail for us would be to have a genomic biomarker or some biomarker that would identify patients who are most at risk for developing brain metastases. At this time, we simply don’t have a biomarker, so we have to treat everyone as if they’re at risk for developing brain metastases. I wouldn’t say that we, at this time, treat anyone differently until diagnosis of brain metastasis has occurred. We don’t, at this time, do screening MRIs in those patients, and it’s unclear if doing a screening MRI and identifying an asymptomatic brain metastasis early would affect outcomes. Those are questions to be answered in the future.

Bhavesh Shah, RPh, BCOP: Because patients with metastatic breast cancer with brain metastases could have asymptomatic brain metastases, how do you drive value for those patients? It goes into what happens to those patients if they don’t receive treatment: They’re going to have CNS progression. The time to delay in that CNS progression for those asymptomatic patients is probably the most important aspect because once they have that progression, that means they will require anticancer cancer therapy. They may require 1 of the TKIs [tyrosine kinase inhibitors], or they may require whole-brain radiation because the lesions are too large and patients are too symptomatic by that time. Preventing the progression of distant metastases for those asymptomatic patients is the value driver.

Clinical pathways are something for which there is big hype, right? Everybody has a pathway that they’re using. There are probably at least 7 or 8 different companies that offer pathways. Payers have pathways. The term is also loose because institutions have formularies that have pathways, and we control our formulary through our electronic medical record by having order sets for how we treat each disease.

For HER2-positive metastatic breast cancer, there are first-line agents that we would utilize, there are second-line agents, and there are third-line agents. Of course, as you progress through the lines of therapy, there are probably more options that you have, but we need to work with our providers to develop these based on consensus. We also use NCCN [National Comprehensive Cancer Network] and ASCO [American Society of Clinical Oncology] Guidelines to drive these types of pathways in our electronic medical record. The short answer is that we internally develop our own pathways through our experts in breast cancer in collaboration with national guidelines.