Phase I study of local radiation and tremelimumab in patients with inoperable locally recurrent or metastatic breast cancer
Metrics: PDF 245 views | HTML 808 views | ?
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
|Srikala S. Sridhar,||email:||Srikala.firstname.lastname@example.org|
Keywords: radiation; immunotherapy; breast cancer; anti-CTLA-4
Received: January 22, 2019 Accepted: April 14, 2019 Published: April 26, 2019
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.