PracticeUpdate Oncology Best of 2018

EXPERT OPINION 21

PracticeUpdate: Dr. Hurvitz, will you talk about your current approach to patients with HER2-positive breast cancer and brain metastases? Dr. Hurvitz: For a patient who has brain metastases and who is HER2-positive, we first have to look and see if there is disease outside the CNS. If a patient has disease that is progressing below the neck, we should be using standard systemic therapy which we would otherwise use for metastatic HER2-positive breast can- cer. For example, if the patient had received trastuzumab-based therapy and had progressed on that, our next treatment would be TDM-1; so, we base our systemic therapy recommendations on whether or not the patient’s disease below the neck is controlled. If the patient’s disease is controlled below the neck, we should continue the therapy that we are using systemically, and then we can use local measures to control the CNS metastases – for example, surgery, stereotactic radiosurgery, radiation therapy, and so on – and usually we recommend that patients are seen at a multidisciplinary tumor board where they meet with a neurosurgeon and radiation oncologist to discuss the best way of managing the disease. The way that we treat it going forward may evolve as more agents that penetrate the CNS and demonstrate activity there are devel- oped. So, hopefully, drugs like tucatinib and other drugs that cross the blood–brain barrier will become available. However, to date, we don’t make systemic therapy recommendations based on CNS metastases. PracticeUpdate: And what are the current data on everolimus for brain metastases? Dr. Hurvitz: We conducted a study looking at everolimus in combi- nation with lapatinib and capecitabine in patients whose disease, HER2-positive breast cancer, had progressed in the CNS. These patients were pretty heavily pretreated, and, in fact, many of them had already received lapatinib and capecitabine but none of them had received everolimus. We did a phase I dose-escalation trial to define the safe dose because giving these three drugs in combination could cause diarrhea and mucositis. So, we defined a safe dose and then, in the phase II portion, enrolled patients at that dose. We enrolled about 19 patients on this small clinical trial and demonstrated an objective response rate of 27%. There are other studies that have had early results reported looking at everolimus in combination with other chemotherapy and trastuzumab, and the publication of those results are eagerly awaited. PracticeUpdate caught up with Dr. Sara Hurvitz, Director of the Breast Oncology Program at the UCLA Jonsson Comprehensive Cancer Center in Los Angeles, California, at the Miami Breast Cancer Conference. Dr. Sara Hurvitz on Management of HER2- Positive Breast Cancer With Brain Metastases Interview with Sara A. Hurvitz MD

PracticeUpdate: Have you ever used intrathecal trastuzumab? What are your thoughts about this? Dr. Hurvitz: I have used intrathecal trastuzumab on occasion. A number of case reports are published relating to different dos- ing schedules. It’s generally well-tolerated. I personally have not seen any benefits in patients with parenchymal brain metasta- ses; but, in those patients with leptomeningeal metastases who are HER2-positive, I’ve seen the disease stabilize in a handful of cases. We have it available to some of our patients. I’m hoping that down the line we’ll have more effective therapies available for this type of disease. PracticeUpdate: So, it seems that there are several drugs in the pipe- line, as you mentioned, tucatinib and also maybe abemaciclib. We will be able to use them in the future? Dr. Hurvitz: Yes; well, investigation of tucatinib is ongoing in a phase II randomized study. They are allowing patients on this study with progressing CNS metastases, and they are also allowing patients who don’t have CNS metastases. Hopefully that study will show positive results. It’s a blinded study, so we don’t know, but the phase I data of tucatinib showing an objective response rate in the brain of 42% is pretty exciting; I think we’re all looking forward to that. Abemaciclib does penetrate the blood–brain barrier, but whether or not it’s going to be active in HER2- positive CNS metas- tases has not been fully explored to date. There are only a handful of patients who were treated in the study looking at that. www.practiceupdate.com/c/65218

VOL. 2 • NO. 4 • 2018