Addition of GM-CSF to trastuzumab stabilises disease in trastuzumab-resistant HER2+ metastatic breast cancer patients

BACKGROUND: One of the proposed mechanisms of trastuzumab-induced regression of human epidermal growth factor receptor 2-positive (HER2+) tumours includes facilitation of antibody-dependent cell-mediated cytotoxicity (ADCC). Granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates ADCC. We presented our pilot study of adding GM-CSF to trastuzumab in patients with trastuzumab-resistant HER2+ metastatic breast cancer. METHODS: Patients with HER2+ metastatic breast cancer that progressed after trastuzumab +/− chemotherapy were continued on trastuzumab 2 mg kg(–1) intravenous weekly and GM-CSF 250 μg m(–2) subcutaneous daily. Patients were assessed for response every 8 weeks. Treatment was continued until disease progression or intolerable toxicity. RESULTS: Seventeen patients were evaluable (median age 48 years, range 27–75 years). The median number of metastatic sites was 2 (range 1–3); the most common site was the liver (n=10). The median number of prior regimens for metastatic disease was 2 (range 1–5). No objective disease response was observed, but five patients (29%) had stable disease for a median duration of 15.8 (range 10–53.9) weeks. The most common adverse event was rash at the injection site. No grade 4 or irreversible adverse event was seen. CONCLUSION: The addition of GM-CSF to trastuzumab alone had a modest clinical benefit and acceptable safety profile in heavily pretreated patients with trastuzumab-resistant HER2+ metastatic breast cancer.