Radiosensitization of Chemotherapy-Refractory, Locally Advanced or Locally Recurrent Breast Cancer With Trastuzumab: A Phase II Trial
Presented at the 48th American Society for Therapeutic Radiology and Oncology Annual Meeting, November 5–9, 2006, Philadelphia, PA.
Received 26 November 2008; received in revised form 5 March 2009; accepted 12 March 2009. published online 29 June 2009.
Purpose
Trastuzumab (Herceptin), an anti-human epidermal growth factor receptor 2 (HER2) antibody, has been shown to be an effective radiosensitizer in preclinical studies. The present Phase II trial evaluated trastuzumab plus radiotherapy in patients with HER2-positive, chemotherapy-refractory, locally advanced or locoregionally recurrent breast cancer.
Methods and Materials
Eligible patients had measurable disease, normal cardiac function, and biopsy-confirmed residual HER2-positive disease. Patients received weekly trastuzumab (2 mg/kg intravenously), concurrent with radiotherapy (50 Gy) to the breast and regional lymph nodes for 5 weeks. If feasible, surgery followed radiotherapy. The primary endpoint was safety, and the secondary endpoint was efficacy (pathologic response and interval to symptomatic local progression).
Results
Of the 19 patients enrolled, 7 were ineligible and received radiotherapy alone and 12 received therapy per protocol. Of these 12 patients, 11 had a Stage T4 diagnosis. Grade 3 toxicities included skin (n = 2) and lymphopenia (n = 1). One patient experienced delayed wound healing after surgery. No patients developed symptomatic cardiac dysfunction. Of the 7 patients who had undergone mastectomy, 3 (43%) had a substantial pathologic response (complete response or microscopic residual disease), significantly more than a comparison cohort (2 of 38 or 5%, p = .02). The median interval to symptomatic local progression was not reached. The median overall survival was 39 months.
Conclusion
This is the first prospective trial providing evidence for a radiosensitizing effect of trastuzumab in breast cancer. The combination of trastuzumab and radiotherapy was well tolerated.
∗Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC
‡Department of Internal Medicine, Division of Hematology and Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC
§Department of Surgery, Division of Surgical Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC
†Lineberger Comprehensive Cancer Center, Chapel Hill, NC
Reprint requests to: Janet K. Horton, M.D., Department of Radiation Oncology, Duke University Medical Center, DUMC 3085, Durham, NC 27710. Tel: (919) 668-5213; Fax: (919) 668-7345
Support and third-party writing assistance provided by Genentech USA, Inc., South San Francisco, CA.
ABSTRACT