A Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer |
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| Affiliation: | 1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;2. Harvard Medical School, Boston, MA;3. Current affiliation: Oncology Center, Hospital Sírio-Libanês, Brasília, Brazil;4. Department of Pathology, Brigham and Women’s Hospital, Boston, MA;5. Division of Breast Surgery, Department of Surgery, Brigham and Women''s Hospital; Breast Oncology Program, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA;6. Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA;1. Division of Surgical Oncology, Department of Surgery, University of California, Davis, Medical Center, Sacramento, CA;2. Department of Emergency Medicine, University of California, Davis, Medical Center, Sacramento, CA;1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts;2. Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts;3. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts;4. Department of Imaging, Dana-Farber Cancer Institute, Boston, Massachusetts;6. Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts;5. Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts;7. Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts;11. Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts;1. Division of Research and Clinical Medicine, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia;2. IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA;3. Institute Jules Bordet, Brussels, Belgium;4. Centre Léon Bérard, Lyon, France;5. Westmead Hospital and the University of Sydney, Sydney, NSW, Australia;6. University of Milano, Milan, Italy;7. IEO, European Institute of Oncology IRCCS, Milan, Italy;8. Institut de Cancérologie de l''Ouest, Saint-Herblain, Nantes, France;9. Ospedale di Prato—AUSL Toscana Centro, Prato, Italy;10. Institut Bergonié Comprehensive Cancer Center, Université de Bordeaux, Bordeaux, France;11. International Breast Cancer Study Group, CHU Liège, Liège University, Liège, Belgium;12. Medical University of Vienna, Vienna, Austria;13. University Hospital Inselspital, Bern, Switzerland;14. International Breast Cancer Study Group Coordinating Center, Bern, Switzerland;15. International Breast Cancer Study Group and Central Pathology Office, Bern, Switzerland;p. QIMR Berghofer Medical Research Institute, Herston, QLD, Australia;q. International Breast Cancer Study Group and Ospedale di Prato–AUSL Toscana Centro, Prato, Italy;r. International Breast Cancer Study Group and Division of Medical Senology, IEO, European Institute of Oncology IRCCS, Milan, Italy;s. Harvard Medical School, Boston, MA, USA;t. Institut Gustave Roussy, Université Paris Sud, INSERM U981, Villejuif, France;1. Weill Cornell Medical College, New York, NY, USA;2. USC Keck School of Medicine, Los Angeles, CA, USA;1. Department of Radiation Oncology, Brigham and Women''s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts;4. Harvard Radiation Oncology Program, Brigham and Women''s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts;3. Harvard Medical School, Boston, Massachusetts;6. Department of Medical Oncology and Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts;2. Division of Radiation Oncology, University of Ottawa, Ottawa, Ontario, Canada;1. Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL, USA;2. Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, USA |
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| Abstract: | ![]()
BackgroundThe purpose of this study was to investigate whether combining pembrolizumab with palliative radiation therapy (RT) improves outcomes in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC).Patients and MethodsEligible patients had HR+/human epidermal growth factor receptor 2-negative MBC; were candidates for RT to ≥ 1 bone, soft tissue, or lymph node lesion; and had ≥ 1 lesion outside the RT field. Patients received 200 mg pembrolizumab intravenously 2 to 7 days prior to RT and on day 1 of repeating 21-day cycles. RT was delivered to a previously unirradiated area in 5 treatments each of 4 Gy. The primary endpoint was objective response rate. The study used a 2-stage design: 8 women were enrolled into the first stage, and if at least 1 of 8 patients experienced an objective response, 19 more would be enrolled. Secondary endpoints included progression-free survival, overall survival, and safety. Exploratory endpoints included association of overall response rate with programmed death-ligand 1 status and tumor-infiltrating lymphocytes.ResultsEight patients were enrolled in stage 1. The median age was 59 years, and the median prior lines of chemotherapy for metastatic disease was 2. There were no objective responses, and the study was closed to further accrual. The median progression-free survival was 1.4 months (95% confidence interval, 0.4-2.1 months), and the median overall survival was 2.9 months (95% confidence interval, 0.9-3.6 months). All-cause adverse events occurred in 87.5% of patients, including just 1 grade 3 event (elevation of aspartate aminotransferase).ConclusionsRT combined with pembrolizumab did not produce an objective response in patients with heavily pre-treated HR+ MBC. Future studies should consider alternative radiation dosing and fractionation in patients with less heavily pre-treated HR+ MBC. |
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| Keywords: | Checkpoint blockade Immune checkpoint inhibitor Immunotherapy PD-1 inhibitor Radiation |
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