Although a consistent effect was observed across most subgroups, in an exploratory analysis, evidence of survival benefit was not observed in women (HR 0

Although a consistent effect was observed across most subgroups, in an exploratory analysis, evidence of survival benefit was not observed in women (HR 0.98, 95% CI 0.77-1.25). effect was observed across most subgroups, in an exploratory analysis, evidence of survival benefit was not observed in women (HR 0.98, 95% CI 0.77-1.25). The reason for this is unclear, but it may be explained by the fact that more women were receiving second-line chemotherapy in the PC arm, although there was no difference in the subsequent use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs). There might also be imbalances between the two groups with respect to known or unknown prognostic factors; there was a higher incidence of liver metastases in women receiving bevacizumab. Given that smoking history is usually a predictive factor for the efficacy of EGFR inhibitors,4 the lack of this important data in this study complicated the interpretation of the potential impact of subsequent EGFR-TKIs around the clinical outcome. Additionally, because female patients with advanced NSCLC showed significantly longer survival, regardless of any treatment, they might derive little additional benefit, if CD69 any, from a bevacizumab-containing regimen. In a second large phase III trial (AVAiL),3 comparing cisplatin/gemcitabine (CG) alone versus CG in combination with bevacizumab (7.5 or 15 mg/kg) and PFS, the primary end point of the study was significantly longer in both bevacizumab treatment arms compared with the placebo arm. The HR for PFS was 0.75 (= 0.003) for the low-dose bevacizumab arm versus placebo (median PFS, 6.7 versus 6.1 months, respectively) and 0.82 (= 0.03) for the high-dose bevacizumab arm versus placebo (median PFS, 6.5 versus 6.1 months, respectively). Furthermore, the objective RR and median period of response were significantly higher in both bevacizumab arms compared with the placebo arm (30% versus 34% versus 20% in 15 mg/kg, 7.5 mg/kg and placebo arms, respectively). Even though trial was not powered to directly compare the two bevacizumab doses, the results indicate similar efficacy in Furilazole terms of PFS and RR for low- and high-dose bevacizumab arm. However, in a final OS analysis with median 12.5 months follow-up, AVAiL did not demonstrate a significant OS benefit, a secondary endpoint, in the bevacizumab arm (median OS, 13.4 versus 13.6 versus 13.1 months in 15 mg/kg, 7.5 mg/kg and placebo arms, respectively).6 Potential explanations for the discrepancy of OS benefit between E4599 and AVAiL may exist. Firstly, this just indicate that second-line therapies may potentially impact study outcomes. It is critical to recognize that approximately 60% of patients in the AVAiL trial have received subsequent lines of therapy, with approximately 40% of these patients receiving EGFR-TKIs. Interestingly, in an exploratory analysis of the group who did not receive postprotocol therapies, patients receiving bevacizumab showed pattern towards better OS (8.7 versus 7.3 months in placebo arm; HR, 0.84; = 0.20).6 Secondly, the remarkably long median OS in control arm (13.1 months) in AVAiL Furilazole trial might necessitate larger sample size in order to demonstrate statistically significant OS benefit. Thirdly, bevacizumab may be Furilazole more effective with paclitaxel/carboplatin regimen than with gemcitabine/cisplatin regimen. Nevertheless, failure to demonstrate OS benefit in AVAiL, which findings clearly contrast with those of E4599, call into question the magnitude of benefits patients will gain from your addition of bevacizumab to standard chemotherapy. In conclusion, bevacizumab added to palliative chemotherapy has improved PFS in two phase III trials and OS in one of these trials in selected patients with advanced NSCLC. Based on these results, bevacizumab has now been approved in the first-line treatment of nonsquamous NSCLC in many countries. Security and toxicity results In E4599 trial, the rate of hypertension, proteinuria, bleeding, neutropenia, febrile neutropenia, thrombocytopenia, hyponatremia, rash, and headache were significantly higher in the bevacizumab arm than in the control arm.2 There was significantly higher incidence of treatment-related toxic deaths in bevacizumab arm compared with the control arm (4.6% versus 0.5%, = 0.001). The most serious, and sometimes fatal, adverse events (AEs) in patients receiving.