Also for the first line treat ment, the first analysis of a 3 arm randomized trial com paring paclitaxel plus placebo or bevacizumab or motesanib has been recently presented, with a median follow up of 10 months. No significant differences in the pri mary objective of the study, were found between the three arms, ref 3 at the expense of a higher grade 3 and 4 incidence of neutropenia, hepato biliary and gastrointestinal toxicity for patients receiving motesanib. For the second line setting of HER 2 negative patients, a recent trial randomizing patients between capecitabine and sunitinib, did not show any PFS superiority of the tyr osine kinase over capecitabine.

More concerning data with regard to the overall safety profile of bevacizumab have been recently released in the context of a literature based meta analysis evaluating the addition of bevacizumab to chemotherapy or biologics accruing data of more than 10,000 patients regardless of the cancer type, the Inhibitors,Modulators,Libraries rate of treatment related mortality was significantly higher in the experi mental arm. Deaths seem to be associated with hemorrhage, neutropenia and gastrointestinal perfora tion, with a significant interaction according to the che motherapeutics combined. With specific regard to breast cancer, a further meta analysis recently showed a statistically sig nificant higher risk of heart failure with bevacizumab, both meta analyses report no interaction according to the bevacizumab dose as a common finding.

Although all these data require an individual patient data analysis for the competitive death risk evaluation, in order to clearly correlate the adverse events together, and even taking Inhibitors,Modulators,Libraries into account Inhibitors,Modulators,Libraries the heterogeneity across all studies and settings, many concerns still remain for the wide adoption of this agents. Conclusions Our data in context with the other exploring the safety Inhibitors,Modulators,Libraries efficacy balance of the addition of bevacizumab to che motherapy for advanced breast cancer do strengthen the need of a deep analysis of the correlation between adverse events and deaths on one side, and the maximi Inhibitors,Modulators,Libraries zation of the efficacy by restricting the drug to those patients who will really benefit. The latest approach is far to be understood, although positive hints with regard to polymorphisms analyses are encouraging. Bevacizu mab, from a clinical practice standpoint, slightly increases the efficacy of chemotherapy in HER 2 nega tive advanced breast cancer, although a close follow up monitoring for adverse events must be adopted. Background Cancer diagnostics and treatment are being revolution ized by the inhibitor licensed clinical application of information generated during the past three decades of basic cancer research.