Cuppone et al. Journal of Experimental & Clinical Cancer Research 2011, 30:54 http://www.jeccr.com/content/30/1/54 R E S E A R C H Open Access Magnitude of risks and benefits of the addition of bevacizumab to chemotherapy for advanced breast cancer patients: Meta-regression analysis of randomized trials Federica Cuppone1†, Emilio Bria1,2*†, Vanja Vaccaro1, Fabio Puglisi3, Alessandra Fabi1, Isabella Sperduti4, Paolo Carlini1, Michele Milella1, Cecilia Nisticò1, Michelangelo Russillo1, Paola Papaldo1, Gianluigi Ferretti1, Matti Aapro5, Diana Giannarelli4 and Francesco Cognetti1 Abstract Background: Although the addition of bevacizumab significantly improves the efficacy of chemotherapy for advanced breast cancer, regulatory concerns still exist with regard to the magnitude of the benefits and the overall safety profile. Methods: A literature-based meta-analysis to quantify the magnitude of benefit and safety of adding bevacizumab to chemotherapy for advanced breast cancer patients was conducted. Meta-regression and sensitivity analyses were also performed to identify additional predictors of outcome and to assess the influence of trial design. Results: Five trials (3,841 patients) were gathered. A significant interaction according to treatment line was found for progression-free survival (PFS, p = 0.027); PFS was significantly improved for 1st line (Hazard Ratio, HR 0.68, p < 0.0001), with a 1-yr absolute difference (AD) of 8.4% (number needed to treat, NNT 12). A non-significant trend was found in overall survival (OS), and in PFS for 2nd line. Responses were improved with the addition of bevacizumab, without interaction between 1st line (Relative Risk, RR 1.46, p < 0.0001) and 2nd line (RR 1.58, p = 0.05). The most important toxicity was hypertension, accounting for a significant AD of 4.5% against bevacizumab (number needed to harm, NNH 22). Other significant, although less clinically meaningful, adverse events were proteinuria, neurotoxicity, febrile neutropenia, and bleeding. At the meta-regression analysis for 1st-line, more than 3 metastatic sites (p = 0.032), no adjuvant chemotherapy (p = 0.00013), negative hormonal receptor status (p = 0.009), and prior anthracyclines-exposure (p = 0.019), did significantly affect PFS. Conclusions: Although with heterogeneity, the addition of bevacizumab to 1st-line chemotherapy significantly improves PFS, and overall activity. Hypertension should be weighted with the overall benefit on the individual basis. Introduction Breast cancer is the cancer with the highest incidence in women, and the major cause of death worldwide [1,2]. About 6% of patients with breast cancer present with advanced disease ab initio, while 40% of patients with loca- lized disease subsequently develop distant metastases [2]. * Correspondence: emiliobria@yahoo.it † Contributed equally 1Department of Medical Oncology, Regina Elena National Cancer Institute, Roma, Italy Full list of author information is available at the end of the article Despite numerous advances in early diagnosis and treatment in local and systemic, metastatic breast cancer remains an incurable disease and the main objective of therapy is both the prolongation of survival and the improvement of associated symptoms (palliative intent), with particular reference to delay the onset of symptoms, improvement in progression-free survival (dominant clin- ical endpoint used to support marketing authorizations in this setting), and improvement of quality of life [3]. Metastatic breast cancer is a heterogeneous disease whose evolution is difficult to predict. Choosing the best © 2011 Cuppone et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.