Oncotarget

Research Papers:

Phase I study of local radiation and tremelimumab in patients with inoperable locally recurrent or metastatic breast cancer

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Oncotarget. 2019; 10:2947-2958. https://doi.org/10.18632/oncotarget.26893

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Di (Maria) Jiang, Anthony Fyles, Linh T. Nguyen, Benjamin G. Neel, Adrian Sacher, Robert Rottapel, Ben X. Wang, Pamela S. Ohashi and Srikala S. Sridhar _

Abstract

Di (Maria) Jiang1, Anthony Fyles2, Linh T. Nguyen3, Benjamin G. Neel3,6, Adrian Sacher1, Robert Rottapel3, Ben X. Wang3, Pamela S. Ohashi3,4,5 and Srikala S. Sridhar1

1 Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada

2 Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada

3 Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada

4 Department of Immunology, Faculty University of Toronto, Toronto, Canada

5 Department of Medical Biophysics, University of Toronto, Toronto, Canada

6 Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA

Correspondence to:

Srikala S. Sridhar,email: Srikala.sridhar@uhn.ca

Keywords: radiation; immunotherapy; breast cancer; anti-CTLA-4

Received: January 22, 2019     Accepted: April 14, 2019     Published: April 26, 2019

ABSTRACT

Immunotherapy has shown modest activity in metastatic breast cancer (MBC). In this phase I dose escalation study, we assessed safety of tremelimumab, a humanized anti-CTLA4 monoclonal antibody, at starting dose 3 mg/kg, on the third day of palliative radiotherapy (2000cGy in 5 daily fractions) in patients with MBC. Primary objective was to determine the maximum tolerated dose (MTD) of tremelimumab combined with RT. Secondary objective was to assess response. Among 6 patients enrolled between July 2010 and October 2011, 5 had hormone receptor-positive MBC, 1 had triple negative MBC. Median age was 45 years. Common toxicities included lymphopenia (83%), fatigue (50%) and rash (33%). One dose-limiting toxicity occurred at 6 mg/kg, however the trial closed before MTD could be determined. One patient discontinued treatment due to a pathological fracture. Best response was stable disease (SD), 1 patient had SD for >6 months. Median follow up was 27.0 months. Median OS was 50.8 months, with 1 patient surviving >8 years. Peripheral blood mononuclear cell (PBMC) profiles showed increasing proliferating (Ki67+) Treg cells 1 week post treatment in 5 patients. Overall, tremelimumab at 3 mg/kg combined with RT appears to be a tolerable treatment strategy. Further studies are needed to optimize this combination approach.



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