Metronomic chemotherapy combined with bevacizumab and erlotinib in patients with metastatic HER2-negative breast cancer: Clinical and biological activity

Background: The 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 Methods: Patients 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). Results: Of 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). Conclusion: Treatment with metronomic chemotherapy in combination with bevacizumab and erlotinib was effective in HER2^-, estrogen receptor (ER)- and progesterone receptor (PR)-poor advanced breast cancer.