Oncotarget

Research Papers:

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

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 _

PDF  |  HTML  |  Supplementary Files  |  Order a Reprint

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

Metrics: PDF 135 views  |   HTML 333 views  |   ?  


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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 26893