Assistant Attending Physician
Memorial Sloan Kettering Cancer Center
New York, NY
Co-Investigator: Jedd Wolchok, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, NY
Brain metastasis is a relatively common and devastating complication of breast cancer. Unfortunately, the treatment of breast cancer brain metastases with conventional drug therapies has been largely unsuccessful primarily due to the poor penetration across the blood-brain-barrier. Furthermore, brain metastasis can be more resistant to chemotherapy than systemic metastasis. Consequently, radiotherapy techniques such as whole brain radiation therapy (WBRT) and stereotactic radiosurgery remain the cornerstone of brain metastases management for most patients. There is a growing body of preclinical and clinical evidence indicating that the local effects of radiotherapy may be augmented when combined with immunotherapy. There is also some data indicating that radiotherapy administered in combination with immune therapy may confer benefits not only at the site of radiotherapy administration but also at distant sites of metastases.
Because of the growing body of compelling data in support of strategies that combine immune system modulation with radiotherapy, Drs. McArthur and Wolchok will conduct a randomized phase 2 study of WBRT with or without immune therapy with tremelimumab, a fully human anti-CTLA4 antibody, in women with hormone receptor-positive (HR+) or HER2-positive (HER2+) breast cancer metastases to the brain.
The central goal for this project is to make a major advance for women with breast cancer brain metastases (BCBM) by answering the research question, “Can local tumor-specific immune stimulation with brain radiotherapy (RT) be augmented by systemic immune modulation and, in turn, lead to specific and durable local and distant antitumor responses?” Since the BCRF grant was awarded the researchers have further developed and strengthened their study strategy. Specifically, because the proposed strategy of combined therapy with brain radiation and immune stimulation has not previously been evaluated in breast cancer, and because it is not known whether any breast cancer subtype is more likely than another to respond to this strategy, they have developed a two-step strategy to explore the research question. The first step will now be a small pilot study that will: 1) confirm the safety of combined therapy with immune modulation and brain RT 2) provide a signal about systemic disease control by evaluating responses at distant sites of disease (i.e. beyond the brain) at 12 weeks 3) allow patients a potentially clinically meaningful respite from chemotherapy 4) include all breast cancer subtypes 5) provide safety data for concurrent trastuzumab administration in HER2-positive disease 6) include both stereotactic radiosurgery (SRS) and whole brain RT (WBRT) modalities and 7) permit exploratory correlative studies. By adding the step of a brief pilot study that is broadly inclusive, the research team will better inform the final design of the second step, namely the randomized phase 2 study that formed the foundation of their original grant application. To that end, they have since developed a protocol entitled, “A Pilot Study of Brain Irradiation and Tremelimumab in Metastatic Breast Cancer” which is currently pending institutional approval and should be open to accrual in early 2014.
Dr. Heather McArthur, MPH, is a medical oncologist at Memorial Sloan Kettering Cancer Center with a clinical practice dedicated to the care of patients with breast cancer. Her research activities are focused on innovations in the diagnosis and treatment of breast cancer. For example, she is currently evaluating the impact of tumor destruction with freezing (cryoablation) in combination with immune stimulation for the treatment of women with early stage breast cancer. It is hoped that by augmenting one's immune response to the unique biologic features of one's tumor, that an effected individual may develop long-term immunity against their tumor, and thus, be cured of her disease.
Dr. McArthur completed formal medical oncology training at the University of British Columbia. There, she was awarded the highly competitive Canadian Association of Medical Oncology/Canadian Institute for Health Research R&D Fellowship which funded her advanced clinical research fellowship at MSKCC. She has a master’s degree in Public Health from Harvard University with a concentration in Clinical Effectiveness. She has presented her research many times at the American Society of Clinical Oncology (ASCO) Annual Meeting and the San Antonio Breast Cancer Symposium and her research has been acknowledged by numerous research awards. She has served on the Conquer Cancer Foundation of ASCO YIA/CDA Grants Selection Committee, the ASCO Breast Cancer Symposium Program Committee, and a National Cancer Institute Breast Cancer Steering Committee Working Group. She has been a reviewer for several clinical journals including Nature Clinical Practice Oncology, the Journal of Clinical Oncology, Cancer, and Clinical Breast Cancer. Dr. McArthur has written more than 50 articles, review articles, invited commentaries, and book chapters on breast cancer.