Paclitaxel and Bevacizumab as First Line Combined Treatment in Patients with Metastatic Breast Cancer: The Hellenic Cooperative Oncology Group Experience with Biological Marker Evaluation

[摘要]：Background: Randomized studies have shown that bevacizumab combined with taxane-based regimens increases response rates and prolongs progression-free survival (PFS) of patients with metastatic breast cancer (MBC). However predictive or prognostic biological markers that identify the appropriate target population, thus improving the cost-effectiveness ratio of this treatment, are still needed. Patients and Methods: Retrospectively, 124 patients with MBC treated either with paclitaxel 90 mg/m(2) weekly x12 plus bevacizumab 10 mu g/kg every 2 weeks or 15 mu g/kg every 3 weeks (85 patients) or paclitaxel 175 mg/m(2) plus bevacizumab 15 mu g/k every 3 weeks for 6 cycles (36 patients) were identified. Additionally, the prognostic significance of a panel of key biological markers was evaluated centrally by immunohistochemistry (IHC) in 88 evaluable patients. Results: More than two thirds of the patients completed chemotherapy, as planned. The response rate was almost identical (55.3% vs. 55.6%) in the patients treated with weekly or 3-weekly paclitaxel, respectively. After a median follow-up time of 23 months, the median PFS of the study population was 13 months, while median survival had not yet been reached. Common severe adverse events were neutropenia (33%), neuropathy (18.6%) and metabolic disturbances (17.6%). The incidence of hypertension of all grades was 28.1%. High expression of vascular endothelial growth factor (VEGF) receptor 3 (VEGFR3) was associated with clinical response, while high expression of VEGFR1 was associated with poor survival. Conclusion: The safety and activity of the combination of bevacizumab with paclitaxel given either weekly or 3-weekly in patients with MBC is confirmed.

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