Role of Brain Metastases and Quality of Life in Treatment Decisionmaking

EP: 1.Landscape of HER2+ Metastatic Breast Cancer: Patient Overview

EP: 2.HER2+ Metastatic Breast Cancer: An Evolving Treatment Armamentarium

EP: 3.HER2+ Metastatic Breast Cancer: Factors in Selecting 2L Therapy and Beyond

EP: 4.Role of T-DXd in Patients With HER2+ Metastatic Breast Cancer and CNS Metastasis

EP: 5.HER2+ Breast Cancer With CNS or Leptomeningeal Metastases: Future Directions in Care

EP: 6.Patient Profile: A 68-Year-Old Woman With HER2+ Metastatic Breast Cancer

EP: 7.Overview of the HER2+ Metastatic Breast Cancer Treatment Armamentarium

EP: 8.Factors in Selecting Third-Line Therapy for HER2+ Metastatic Breast Cancer

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EP: 9.Role of Brain Metastases and Quality of Life in Treatment Decisionmaking

EP: 10.Addressing Resistance to HER2-Targeted Therapy in Metastatic Breast Cancer

EP: 11.HER2+ Metastatic Breast Cancer: Unmet Needs and Future Directions in Care

Transcript:

Virginia Kaklamani, MD, DSc: HER2+ breast cancer is the most common cancer to go to the brain, and we're still struggling with why this is the case. This cancer has affinity for the brain and around 50% of our patients with metastatic HER2+ breast cancer will develop brain metastases at some point. The most likely time for them to develop them is at that second-line therapy, so after initial progression of disease. So, then what do we do? First, we must differentiate between active and stable brain metastases, and how do we define that? If we have newly developed brain metastases or brain metastases that are now growing, that's called the active brain metastases. In that case, the only agent that has been studied in a phase 3 clinical trial setting is tucatinib. Now, if we have brain metastases that are treated and are stable, then we call that stable brain metastases. In many of these clinical trials in HER2+ disease have allowed the participation of patients with stable brain metastases. We have a lot of agents to consider. The question is, is there some agent that's better than another in patients with brain metastases? And what we need to consider is the blood brain barrier. We know that patients that have brain metastases have some destruction of the blood brain barrier, because cancer cells are big cells, so for them to be able to enter the brain, that blood brain barrier is not intact. In that case, large molecules such as antibody drug conjugates, can enter the blood brain barrier, because it's not intact and therefore they can treat patients with brain metastases. I don't think that there's an agent that is preferentially active in brain mets [metastases] versus another, but that the most active agent is also going to be active in patients with brain mets, and the least active agent is not going to be as active. I will typically try to treat patients with localized therapy such as stereotactic radiosurgery, whole brain radiation, and try to avoid it, but now with hippocampal avoidance—which helps preserve the brain function, especially in our young patients—patients with a good performance status we expect them to live for a long time, and potentially surgery to remove at least the dominant brain metastases. After we do that, I typically give my systemic therapy, then if we see progression in brain disease, I see if I can continue treating it with localized therapies. If I can do that, great, if I can't, then I switch my systemic therapies to try to use another therapy that may be active with a brain metastases.

When we treat a patient with metastatic breast cancer we have 2 goals: having the patient live longer and having the patient live better; better their quality of life. We must achieve both at the same time, but this can be hard because our treatments have adverse events while treating the cancer and improving some symptoms related to the cancer. Quality of life is extremely important, especially in HER2+ disease where we have our patients that live for more than 5 years. Sometimes we can cure patients with metastatic HER2+ breast cancer. Picking a treatment that is well tolerated is extremely important because, as I describe it to my patients, this is a marathon, it's not a sprint. So, giving a lot of treatment upfront and causing a lot of toxicity may prevent us from being able to give treatment later. That is extremely important because we have many options for our patients. Some of these trials are treating patients in the eleventh-line setting, so these patients are going to get a lot of treatment and we need to somehow pace ourselves to be able to provide control of the disease without compromising the quality of life. I use the data from quality of life studies in the clinical trials because these are extremely helpful, and help guide our decision-making.

Transcript edited for clarity.