MedWire News: A small trial of women with locally advanced breast cancer has revealed that trastuzumab may improve the efficacy of radiotherapy without increasing operative morbidity or radiotherapy-related toxicity.
“Trastuzumab… an anti-human epidermal growth factor receptor 2 (HER2) antibody, has been shown to be an effective radiosensitizer in preclinical studies,” explain Janet Horton (Duke University Medical Center, Durham, North Carolina, USA) and colleagues.
To investigate further, Horton and team initiated a phase II clinical trial of trastuzumab plus radiotherapy in 12 patients with locally advanced HER2-positive breast cancer who had had a less than a partial response to neoadjuvant chemotherapy or had locoregionally recurrent disease.
The patients received weekly trastuzumab (2 mg/kg intravenously), concurrent with radiotherapy (50 Gy) to the breast and regional lymph nodes for 5 weeks. Where feasible, radiotherapy was followed by surgery. The primary endpoint of the study was safety, and the secondary endpoint was efficacy.
The researchers report that no patient required treatment interruption because of toxicity. Two patients suffered acute Grade 3 skin toxicity. One of these patients also had Grade 3 lymphopenia and protracted wound healing after mastectomy. No patient developed symptomatic cardiac dysfunction.
Seven patients underwent mastectomy. Of these, two (28%) had a complete pathologic response and one (14%) had a substantial response with only microscopic residual disease. Horton and team note that the pathologic response rate was significantly better than that of a comparison cohort of historic controls that had a response rate of only 5% (two of 38 patients).
The median overall survival was 39 months and the median interval to symptomatic local progression was not reached.
“Although any conclusions are clearly limited because of the low patient numbers, our results may provide the first clinical evidence for a radiosensitizing effect of trastuzumab in breast cancer,” write Horton and co-authors in the International Journal of Radiation Oncology Biology Physics.
They add: “Our ongoing trials in this area will assess the radiosensitizing effect of HER1/HER2 inhibitors, such as lapatinib. In addition, we are investigating the use of other types of radiosensitizers for tumors that are not driven by HER1 or HER2.”
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