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Oncotarget. 2019 Apr 26;10(31):2947-2958. doi: 10.18632/oncotarget.26893. eCollection 2019 Apr 26.

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

Author information

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
Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA.
5
Department of Immunology, Faculty University of Toronto, Toronto, Canada.
6
Department of Medical Biophysics, University of Toronto, Toronto, Canada.

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.

KEYWORDS:

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

Conflict of interest statement

CONFLICTS OF INTEREST Dr. Neel: Co-founder, member of board of directors, consulting and equity in Northern Biologics Co-founder, chair of scientific advisory board, consulting and equity in Navire pharma Spouse has equity in Pfizer. Dr. Sacher: Consultant/advisory board for AstraZeneca, Pfizer, Bayer, Gritstone Oncology, Merck, Genentech-Roche Honoraria from AstraZeneca, Pfizer, Bayer, Merck, Genentech-Roche.

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