Metronomic Chemotherapy Combined With Bevacizumab and Erlotinib in Patients With Metastatic HER2-Negative Breast Cancer: Clinical and Biological Activity

BackgroundThe object of this study was to evaluate the safety and efficacy of metronomic chemotherapy in combination with bevacizumab and erlotinib in patients with HER2-negative (HER2−) metastatic breast cancer (MBC) and poor hormone receptor expression.Patients and MethodsPatients with untreated MBC were candidates to receive metronomic oral capecitabine (500 mg thrice daily) and cyclophosphamide (50 mg daily) plus bevacizumab (15 mg/kg every 3 weeks) and erlotinib (100 mg daily).ResultsOf 24 patients assessable for response, we observed 1 complete response (CR, 4%), 14 partial responses (58%), 5 patients with stable disease greater than 9 weeks' duration (SD, 21%), and 1 patient (4%) with early progression of disease. The overall clinical benefit (CB) (CR + partial response + SD > 24 weeks) was 75% (95% confidence interval [CI], 53%-90%). Median time to progression was 43 weeks (95% CI, 21-69). Patients with low levels of circulating endothelial progenitors (CEPs) at baseline had a significantly improved progression-free survival (PFS). Toxicity was generally mild. Grade 3 toxicity included diarrhea (n = 1), thrombosis (n = 1), and hypertension (n = 2). Grade 2 adverse events included diarrhea (n = 5), hand-foot syndrome (n = 13), and hypertension (n = 4).ConclusionTreatment with metronomic chemotherapy in combination with bevacizumab and erlotinib was effective in HER2−, estrogen receptor (ER)- and progesterone receptor (PR)-poor advanced breast cancer.