Summary
Although various new agents have been developed for the treatment of patients with metastatic breast cancer (MBC), overall survival rates have changed little in the last half century. We conducted meta-analysis to verify the clinical efficacy of bevacizumab for the salvage treatment of MBC. Event-based hazard ratios (HR) with 95% confidence intervals (95% CIs) were derived, and a test of heterogeneity was applied. Four studies, with a total of 2,860 patients, met the inclusion criteria for analysis. The pooled results of clinical efficacies were: HR for progression free survival 0.69 (95% CI, 0.58–0.81, z = 4.54, P <0.001); HR for overall survival 0.92 (95% CI, 0.82–1.03, z =1.44, P = 0.15); and HR for the clinical objective response rate 1.53 (95% CI, 1.37–1.71, z = 7.37, P < 0.001). In terms of overall survival, subgroup analysis demonstrated statistically significant improvement for the bevacizumab combination in the initial therapy subgroup (HR, 0.878; 95% CI, 0.771–0.999, z = 1.98, P = 0.048). Hypertension and proteinura were more common in the bevacizumab combination arm; however, these toxicities were managed with therapy. In conclusion, meta-analysis suggested benefits of a carefully managed bevacizumab-containing salvage regimen for patients with histologically or cytologically confirmed Her-2 negative MBC who have not received previous cytotoxic therapy. This treatment could improve both progression free survival and overall survival rates.
References
Pal SK, Gupta R, Bernstein L, Mortimer J (2008) Lack of survival benefit in metastatic breast cancer with newer chemotherapy agents: The City of Hope cancer experience. 2008 Breast Cancer Symposium abstract 95
Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752
Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874
Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100:8418–8423
Reis-Filho JS, Westbury C, Pierga JY (2006) The impact of expression profiling on prognostic and predictive testing in breast cancer. J Clin Pathol 59:225–231
Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K et al (2005) Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res 11:5678–5685
Hanahan D, Folkman F (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364
Folkman J, Cole P, Zimmerman S (1966) Tumor behavior in isolated perfused organs: in vitro growth and metastases of biopsy material in rabbit thyroid and canine intestinal segment. Ann Surg 164:491–502
Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186
Ferrara N (1999) Role of vascular endothelial growth factor in the regulation of angiogenesis. Kidney Int 56:794–814
Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS et al (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362:841–844
Cobleigh MA, Langmuir VK, Sledge GW, Miller KD, Haney L, Novotny WF et al (2003) A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol 30:117–124
Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17:2815–2834
Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8:16
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188
Miller KD, Chap LI, Holmes FA, Cobleigh MA, Marcom PK, Fehrenbacher L et al (2005) Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 23:792–799
Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA et al (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676
Pivot X, Verma S, Thomssen C, Passos-Coelho JL, Latini L, Ciruelos E et al (2009) Clinical benefit of bevacizumab (BV) plus first-line docetaxel (D) in elderly patients (pts) with locally recurrent (LR) or metastatic breast cancer (MBC): AVADO study. J Clin Oncol 27:15s supple; abstr 1094
Robbert NJ, Dieras V, Glaspy J, Brufsky A, Bondarenko I, Lipatov O et al (2009) RIBBON-1: Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab (B) for first-line treatment of HER-2-negative locally recurrent or metastatic breast cancer (MBC). J Clin Oncol 27:15s supple; abstr 1005
Greenberg PA, Hortobagyi GN, Smith TL, Ziegler LD, Frye DK, Buzdar AU (1996) Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol 14:2197–2205
Dedes KJ, Matter-Walstra K, Schwenkglenks M, Pestalozzi BC, Fink D, Brauchli P, Szucs TD (2009) Bevacizumab in combination with paclitaxel for HER-2 negative metastatic breast cancer: An economic evaluation. Eur J Cancer 45(8):1397–1406
Acknowledgements
None of the authors have potential conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lee, JB., Woo, O.H., Park, K.H. et al. Bevacizumab for salvage treatment of metastatic breast cancer: a systemic review and meta-analysis of randomized controlled trials. Invest New Drugs 29, 182–188 (2011). https://doi.org/10.1007/s10637-009-9310-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10637-009-9310-0