Indeed, the initial 14-17% rate reported in the ECOG-2100 trial should be carefully evaluated, given the adoption of paclitaxel on a weekly basis (with its steroid pre-medication) could have biased the specific toxicity rate. The other significant toxicities seem to occur rarely, and in particular those toxicities supposed to be bevacizumab-related (i.e. proteinuria, bleeding) require INCB28060 clinical trial 175-250 patients to be treated for one to be harmed. From a very practical perspective, in order to weight the relative severities of positive and negative events, breast cancer patients receiving bevacizumab in addition to

chemotherapy have ‘likelihood to be helped and harmed’ (LHH) of 2-20 [36]; that means that patients receiving bevacizumab are from 2 to 20 times more likely to be helped than armed. Recently, other anti-angiogenesis drugs have been studied in randomized trials for locally advanced or metastatic breast cancer [37–39]. In the SOLTI-0701 study, patients randomized to the combination of sorafenib and capecitabine showed a median PFS of 6.4 months, compared to the 4.1 months achieved by the patients who received capecitabine alone (HR 0.58, p = https://www.selleckchem.com/products/srt2104-gsk2245840.html 0.0006)

[38], although with a higher incidence of serious adverse events (hand-foot syndrome 45% versus 13%). A further randomized phase II study evaluated the efficacy and toxicity of sorafenib in addition to paclitaxel Methane monooxygenase compared to paclitaxel plus placebo in patients untreated for metastatic disease, demonstrating a statistically significant improvement in PFS, TTP and responses [39]. Also for the first line treatment, the first analysis of a 3-arm randomized trial learn more comparing paclitaxel plus placebo or bevacizumab or motesanib (small molecule inhibitor of

VEGF tyrosine kinase) has been recently presented, with a median follow up of 10 months [40]. No significant differences in the primary objective of the study (the response rate), were found between the three arms, 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 tyrosine kinase over capecitabine [37]. More concerning data with regard to the overall safety profile of bevacizumab have been recently released [41, 42]: 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 rate of treatment-related mortality was significantly higher in the experimental arm [41, 43].