Paclitaxel and Bevacizumab in First Line-Treatment Patients with HER-2 Negative Advanced Breast Cancer: Who could Benefit?

Background: Angiogenesis is essential for tumor growth and development of metastases in human breast cancer. Randomized studies have shown that bevacizumab (inhibitor of VEGF) 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 markers that identify the appropriate target population, thus improving the cost-effectiveness ratio of this treatment, are still needed. In this retrospective analysis, we investigated the impact of traditional clinical and pathological features in order to identify the subgroups of patients who derive the greatest benefit from antiangiogenic-agents. Patients and methods: Retrospectively, we included consecutive patients treated with bevacizumab (10 mg/Kg on days 1 and 15) and paclitaxel (90 mg/m2, on days 1, 8 and 15) as first-line treatment for HER2-negative MBC at our Institution between June 2007 and December 2012. Results: 33 patients were included. Median age was 50 years (31-68). 78. 8%, 12.1% and 9.1% of patients had luminal B, triple negative and luminal A breast cancer, respectively. 66. 6% of patients had visceral disease. The overall response rate was 31.2%. Median PFS and overall survival (OS) were 7.7 months (range 1. 9-14.0 months) and 95.2 months (range 11.6-205.8 months), respectively. Univariate analysis highlighted a statistically significant relationship between PFS to the first line and the following factors: relapse-free survival (RFS<12 months vs. >12 months; p<0,001), disease control rate (p=0,001), Ca15. 3 reduction of more than 50% from baseline (p=0,03), reduction of LDH from baseline (p=0,02). No significant relationship resulted between PFS and the biological characterization of neoplasia, age, receptor status, Ki-67, nodal status at diagnosis, having carried out a previous (neo) adjuvant chemotherapy (with or without taxane), having visceral disease at time of relapse, the histological evidence of lymph-vascular invasion. At multivariate analysis, RFS was the only confirmed independent prognostic factor (p=0.01; HR=0. 18; 95% CI 0. 04-0.73). Conclusion: Our results confirmed the efficacy and the acceptable toxicity profile of bevacizumab plus paclitaxel as first-line regimen for MBC. RFS may be a useful tool in the clinical practice to select HER-2 negative MBC which may obtain a better prognosis administering this particular regimen.