Bevacizumab In Non-small Cell Lung Cancer Research Articles

Genome-wide DNA methylation signature predict clinical benefit of bevacizumab in non-small cell lung cancer

BackgroundThe efficacy of bevacizumab in non-small cell lung cancer (NSCLC) patients is unsatisfactory, and the selection of suitable patients is still challenging. Given the epigenetic modifications can contribute to an aberrant regulation of angiogenesis and microenvironment, we investigated DNA methylation profiles to determine clinical benefit of bevacizumab in NSCLC patients.MethodsGenome-wide DNA methylation profiling was performed in NSCLC patients treated with chemotherapy in combination with bevacizumab. Patients were divided into better prognosis group (A group) and inferior prognosis group (B group) based on their survival. The difference of methylation patterns and respective functional enrichment analysis were performed between two groups. Prognostic DNA methylation signature for bevacizumab was established with the least absolute shrinkage and selection operator regression analyses. TISIDB database was further used to infer immunological relationship for prognostic related DNA methylation.ResultsTwenty patients were included in this study, and significantly distinct methylation patterns were observed between patients with different prognosis. Related genes of different methylation regions were significantly enriched in the biological process of cell projection assembly, neutrophil mediated immunity, and pathway of VEGFA-VEGFR2 signaling pathway, neutrophil degranulation. A 10-gene DNA methylation signature for prognosis prediction was established with the C-index of 0.76. And host genes of signature were found to be related to the abundance of ActCD4, Th1, ActCD8, NKT and neutrophil cells.ConclusionThe 10-gene DNA methylation signature could serve as a novel biomarker to predict the clinical benefit of bevacizumab therapy and improve this anti-tumor approach for NSCLC patients.

Incidence and risk of thromboembolism associated with bevacizumab in patients with non-small cell lung carcinoma.

Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), is effective for the treatment of advanced non-small cell lung cancer (NSCLC). However, severe adverse events (AEs) have been reported in NSCLC patients treated with bevacizumab. Currently, the contribution of Bevacizumab to thromboembolism is still controversial. We conducted a study to determine the overall risk and incidence of thromboembolism with bevacizumab in NSCLC patients. Electronic databases such as the PubMed, Web of Science and Cochrane Library were searched for related trials. Statistical analyses were conducted to calculate the overall incidence rates, odds ratios (ORs), and 95% confidence intervals (CIs) by using either random-effect or fixed-effect models depending on the heterogeneity. We also used trial sequence analysis (TSA) to verify the pooled result. A total of 3,555 subjects from nine studies were included. The overall incidence of thromboembolism events in NSCLC patients treated with bevacizumab was 4.8% (95% CI: 1.9-7.7%). Without bevacizumab, this incidence was 2.9% (95% CI: 0.6-5.1%). Bevacizumab use was associated with a significantly increased risk in thromboembolism events (OR =1.74; 95% CI: 1.15-2.62; P=0.008). Subgroup analysis based on the doses showed that bevacizumab administered at 15 mg/kg (OR =1.81; 95% CI: 1.14-2.86; P=0.012), but not 7.5 mg/kg (OR =1.32; 95% CI: 0.78-2.24; P=0.296), increased the risk of thromboembolism. Bevacizumab is associated with a significantly increased risk of thromboembolism development in NSCLC patients. It may have dose-toxicity relationship and low dose of bevacizumab may be a better choice for NSCLC patients, with equal efficacy and low hazard of thromboembolism events.

Erlotinib in combination with bevacizumab has potential benefit in non-small cell lung cancer: A systematic review and meta-analysis of randomized clinical trials

ObjectivesA role for erlotinib and bevacizumab as single agents has been established in the treatment of non-small cell lung cancer (NSCLC). However, the efficacy and safety of erlotinib in combination with bevacizumab compared with single agents remain unclear. This meta-analysis aimed to investigate the status of this combined strategy in NSCLC. Materials and methodsWe systematically searched relevant databases for randomized controlled trials (RCTs) on the use of erlotinib plus bevacizumab in NSCLC. The main outcomes analysis reported overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse effects. Random-effects models were used to estimate pooled hazard ratio and relative risk. ResultsTen studies with a total of 2802 participants were eligible for meta-analysis, the results of which suggested erlotinib with bevacizumab failed to significantly enhance either OS (95% CI: 0.87–1.12; P = 0.825) or ORR (95% CI: 0.69–1.67; P = 0.758). Though PFS was modestly improved, there was no statistical significance (5.55 months vs. 4.67 months, 95% CI: 0.63–1.15; P = 0.297). Incidence of rash or diarrhea was higher in the combination group than in the single-agent group. Subgroup analysis showed encouraging OS (95% CI: 0.29–0.69; P < 0.001) in epidermal growth factor receptor (EGFR)-mutant patients treated with combination therapy, no such benefits were found in groups restricting on KRAS status. ConclusionErlotinib plus bevacizumab enhances OS for EGFR-mutant patients, with rash and diarrhea common but acceptable adverse effects. Combination treatment can be recommended as the preferable option for EGFR-mutant patients. Further large-scale, well-designed RCTs are required to confirm our validation.

Left Ventricular Perforation in A Patient with Lung Cancer Treated with Bevacizumab

In addition to traditional chemotherapeutic regimens molecular targeted agents emerged as new therapeutic options for the treatment of non-small-cell lung cancer (NSCLC). These targeted therapies do not have the same systemic adverse effects usually observed with traditional cytotoxic drugs, but feature a specific spectrum of characteristic adverse effects. The humanized monoclonal antibody against the VEGF-A ligand Bevacizumab inhibits angiogenesis. The characteristic toxicities of Bevacizumab include hemorrhage, wound healing complications, gastrointestinal perforation, arterial thromboembolism, and infusion-related hypersensitivity reactions. We present a unique case of a left ventricular wall perforation after myocardial infarction associated with the administration of Bevacizumab in NSCLC. Cardiac MRI follow-up showed regression of the ventricular perforation.

Advances in Bevacizumab Therapy for Non-small Cell Lung Cancer with Brain Metastases

脑部是肺癌最常见的远处器官转移部位之一, 肺癌脑转移的发生率高, 是脑转移性肿瘤中最常见的类型, 同时也是肺癌死亡率居高不下的原因之一。抗肿瘤血管生成治疗已成为肺癌治疗的重要手段之一, 抗血管生成药物贝伐珠单抗也成为继全脑放疗、立体定位放疗和化疗之后肺癌脑转移患者新的治疗选择。目前, 对脑转移的非小细胞肺癌患者应用贝伐珠单抗治疗的临床研究也越来越多, 其安全性和有效性是研究重点。本文就贝伐珠单抗治疗非小细胞肺癌脑转移的研究进展做一综述。

Safety and Effectiveness of Bevacizumab-Containing Treatment for Non–Small-Cell Lung Cancer: Final Results of the ARIES Observational Cohort Study

Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor, was approved by the US Food and Drug Administration for the treatment of advanced non-small-cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel. ARIES (Avastin Regimens: Investigation of Effectiveness and Safety), a prospective observational cohort study, evaluated outcomes in a large, community-based population of patients with first-line NSCLC. From 2006 to 2009, ARIES enrolled patients with locally advanced or metastatic NSCLC who were eligible for bevacizumab, excluding those with predominantly squamous histology. Patients were required to provide informed consent and to have initiated bevacizumab with chemotherapy within 4 months before enrollment. There were no protocol-defined treatments or assessments. The dosing of bevacizumab and chemotherapy, and the choice of chemotherapy regimen, was at the discretion of the treating physician. ARIES enrolled 1967 patients with first-line NSCLC. At study closure, median follow-up was 12.5 months (range, 0.2-65.5). Median age was 65 years (range, 31-93), and 252 patients (12.8%) identified as never smokers. Median progression-free survival was 6.6 months (95% confidence interval, 6.3-6.9), and median overall survival was 13.0 months (95% confidence interval, 12.2-13.8) with first-line bevacizumab plus chemotherapy. Incidences of bevacizumab-associated adverse events (19.7% overall) were consistent with those in randomized controlled trials of bevacizumab in NSCLC. Results from ARIES demonstrate similar outcomes to randomized controlled trials of bevacizumab when added to standard chemotherapy in a real-world patient population with advanced NSCLC.

Economic evaluation of bevacizumab in the treatment of non-small cell lung cancer (NSCLC)

BackgroundDelivering affordable cancer care is becoming increasingly important. Bevacizumab (BEV) is a costly molecular targeted agent effective for a variety of cancer including lung cancer. The objective of this review is to assess published economic evaluation of BEV in the treatment of non-small cell lung cancer (NSCLC).MethodsA literature search in PubMed, Cochrane, and the Health Technology Assessment reports for English-language publications before February 2012 was performed. Studies were independently screened by two reviewers, and eight publications were included in the review. The results of these eight articles were tabulated and all cost estimates were reported in 2011 US dollars.ResultsAmong the eight articles, three were cost studies and five were cost-effectiveness/utility analysis. For first-line treatment, BEV-containing regimen was reported to be the most costly regimen in one study but cost saving when compared with pemetrexed/cisplatin in another study. When compared with other regimens, BEV-containing regimen was reported to be cost effective in two cost-effectiveness studies (incremental cost-effectiveness ratio [ICER] in the range of US$30,318–US$54,317 per life year) but not cost effective in the other three studies (ICER over US$300,000 per life year).ConclusionIn this review of economic evaluation of BEV in the treatment of NSCLC, it was found that the literature was not conclusive on the economic benefit of BEV. The role of BEV in other treatment settings for NSCLC was unknown. Further studies, such as clinical trials with adequate power to compare the efficacy between low dose and high dose BEV, potential impact of predictive biomarkers for BEV, and comprehensive economic evaluation will strengthen the current state of knowledge on the economic value of BEV in NSCLC.

Bevacizumab in non-small-cell lung cancer: a review

Current targeted strategies for cancer focus on the blockade of growth factor receptors and the inhibition of angiogenesis. The VEGF pathway has become an attractive target in multiple malignancies, including lung cancer. Bevacizumab, a monoclonal antibody against VEGF, increased survival in non-small-cell lung cancer (NSCLC) patients when added to standard carboplatin/paclitaxel chemotherapy. The pivotal Phase III study (ECOG 4599) in NSCLC showed longer overall survival: 12.3 versus 10.3 months and a higher median progression-free survival of 6.2 versus 4.5 months when chemotherapy was associated with bevacizumab. Benefits were confirmed in terms of progression-free survival in the European Phase III study (AVAiL). Subsequently, bevacizumab gained US FDA and European Medicines Agengy approval as a first-line therapy for advanced NSCLC. Bevacizumab’s safety profile is well established: most adverse events are mild to moderate and can be managed using standard interventions. This article presents an overview of the current data on bevacizumab for NSCLC.

A daganatos érhálózat mint terápiás célpont nem kissejtes tüdőrákban

Despite developments in conventional (chemo)radiotherapy and surgery, survival of non-small cell lung cancer (NSCLC) patients remains poor. Treatments with targeted molecular drugs offer novel therapeutic strategies. Bevacizumab, a recombinant anti-vascular endothelial growth factor (VEGF) antibody, is the antiangiogenic drug at the most advanced stage of development in the therapy of NSCLC. However, a number of questions and future challenges relating to the use of bevacizumab in NSCLC remain. Furthermore, novel agents targeting the pre-existing NSCLC vasculature (i.e. vascular disrupting agents, VDAs) or multiple tyrosine kinase inhibitors have emerged as unique drug classes delivering promising results in several preclinical and clinical studies. Herein, we review the most recent data using these novel targeted agents either alone or in combination with chemotherapy in NSCLC.

Role of Bevacizumab for the Treatment of Non-Small-Cell Lung Cancer

Advanced-stage non-small-cell lung cancer (NSCLC) is a lethal disease that is treated with combination chemotherapy. Although modest survival benefit has been documented with various platinum-based, two-drug combination chemotherapy regimens, an efficacy plateau has been reached. Bevacizumab, a monoclonal antibody against the vascular endothelial growth factor, is the first molecularly targeted agent that has demonstrated survival advantage when combined with chemotherapy for the treatment of advanced nonsquamous NSCLC. Improvements in all efficacy parameters, including response rate, progression-free survival and overall survival, were noted for advanced nonsquamous NSCLC patients when bevacizumab was added to the combination of carboplatin-paclitaxel compared with the same chemotherapy regimen alone. This has opened the door for expanding the role of bevacizumab in earlier stages of the disease with chemotherapy or radiotherapy. The anti-angiogenesis agents, including the monoclonal antibody and vascular endothelial growth factor tyrosine kinase inhibitors, will be among the most important drugs of the present decade. This article discusses the recent data with bevacizumab in NSCLC and its potential application at various stages of NSCLC.

Anti-Vascular Endothelial Growth Factor Monoclonals in Non-Small Cell Lung Cancer

There is an urgent need for new therapies to treat non-small cell lung cancer (NSCLC) because current chemotherapy regimens are of limited effectiveness. The role of vascular endothelial growth factor in promoting tumor angiogenesis, in maintaining existing vasculature, and in resistance to traditional therapies, together with its negative prognostic significance in NSCLC, make it an appropriate target for therapy. Bevacizumab (Avastin), a monoclonal antibody directed against vascular endothelial growth factor, has shown promise in treating a number of different cancers. In a recent Phase II trial in patients with advanced metastatic NSCLC, the addition of bevacizumab to standard carboplatin/paclitaxel chemotherapy significantly increased the time to progression and increased the response rate when compared with chemotherapy alone. This was particularly impressive in the subset of patients with non-squamous histology. Bevacizumab is generally well tolerated and did not appear to increase the incidence or severity of nausea/vomiting, neuropathy and renal toxicity, which are typically associated with carboplatin/paclitaxel chemotherapy. Adverse events in Phase I and II studies included hypertension, thrombosis, proteinuria (with occasional nephrotic syndrome), and epistaxis. Serious tumor-related bleeding episodes (hemoptysis/hematemesis) seem to be the main safety concern in patients with NSCLC, with squamous cell histology as a possible risk factor. Present ongoing studies are under way in NSCLC including (a) a Phase II neo-adjuvant study in combination with paclitaxel and carboplatin in patients with stage IB-IIA NSCLC; (b) a Phase I/II study of bevacizumab in combination with the epidermal growth factor receptor tyrosine kinase inhibitor agent, Tarceva, in patients with previously treated NSCLC; and (c) an Eastern Cooperative Group randomized Phase III study of paclitaxel and carboplatin with/without bevacizumab in patients with previously untreated IIIB (malignant pleural effusion) or metastatic NSCLC. These studies will help to establish the role of bevacizumab in NSCLC.

Non-Small Cell Lung Cancer and Antiangiogenic Therapy: What Can Be Expected of Bevacizumab?

There is an urgent need for new therapies to treat non-small cell lung cancer (NSCLC), as progress with current chemotherapy regimens has been limited. The roles of vascular endothelial growth factor (VEGF) in promoting tumor angiogenesis, maintaining existing vasculature, and contributing to resistance to traditional therapies, together with its negative prognostic significance in NSCLC, make it an appropriate target for therapy. Bevacizumab (Avastin; Genentech Inc., South San Francisco, CA), a monoclonal antibody directed against VEGF, has shown promise in treating a number of different cancers. In a recent phase II trial in patients with advanced metastatic NSCLC, the addition of bevacizumab to standard carboplatin/paclitaxel chemotherapy produced a significantly longer time to progression (32.1 versus 18.4 weeks) and greater response rate (31% versus 19% [not significant]) than chemotherapy alone. In the subset of patients with nonsquamous histologies, response rates and survival were further enhanced, with a mean survival time of 17.9 months versus 12.3 months with chemotherapy alone. Bevacizumab was generally well tolerated and did not appear to increase the incidences or severities of the nausea/vomiting, neuropathy, and renal toxicity that are typically associated with carboplatin/paclitaxel chemotherapy. Adverse events in phase I and II studies included hypertension, thrombosis, proteinuria (with occasional nephrotic syndrome), and epistaxis. Serious tumor-related bleeding episodes (hemoptysis/hematemesis) appear to be the main safety concern in patients with NSCLC, with squamous cell histology as a possible risk factor. Further work is needed to identify the best way to use bevacizumab in NSCLC, including use in combination with other biologic agents and in the adjuvant setting.