RADIOSENSITIZATION OF CHEMOTHERAPY-REFRACTORY, LOCALLY ADVANCED OR LOCALLY RECURRENT BREAST CANCER WITH TRASTUZUMAB: A PHASE II TRIAL

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. (C) 2010 Elsevier Inc.