ECOG 4599 PDF

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to paclitaxel/carboplatin, prolongs survival in previously untreated patients with advanced non-small-cell lung cancer: preliminary results from the ECOG Lung Cancer: Secondary Analyses of the ECOG and PointBreak Trials. Eastern Cooperative Oncology Group (E) and PointBreak studies. ECOG demonstrated longer progression-free (PFS) and overall survival ( OS) with the addition of bevacizumab at a dose of 15 mg/m2.

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The median progression-free survival in the two groups was 6. While the meta-analysis was generally well conducted, including the incorporation of tests for heterogeneity of the treatment effect across trials, a few points should be noted.

Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer.

Evidence-based role of bevacizumab in non-small cell lung cancer E. Overall survival with cisplatin—gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: Association between VEGF splice isoforms and progression-free survival in metastatic colorectal cancer patients treated with bevacizumab.

Since then it has been established that gemcitabine is inferior to pemetrexed in non-squamous histology [ 1 ]. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: However, a search for reliable, predictive biomarkers allowing for patient selection continues [ 7 ]. We do not believe so and consider an evidence-based survival benefit to be limited to paclitaxel and carboplatin.

The primary end point was overall survival. In summary, the meta-analysis provided here may not allow us to truly improve our assessment of the role of bevacizumab in combination with chemotherapy for advanced-stage NSCLC.

This meta-analysis seems to suggest possible increased benefits in patients with stage IIIB disease, although it is not clear whether this included patients with stage IIIB disease due to advanced nodal stage or due to pleural effusion.

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As discussed earlier, the paper is also diminished by the fact that individual patient data were not utilized and updates beyond those of the initial database were not carried out.

A number of other anti-angiogenic agents have been investigated in advanced stage NSCLC without success. Exploratory analysis suggested that the doublet maintenance arm might be superior in patients who continued on trial during the maintenance treatment phase, a finding which is consistent with data from other pemetrexed-based maintenance chemotherapy trials [ 2 ].

Its precise contribution to increasing survival remains exog. Of greater clinical interest has been the interaction of pemetrexed with bevacizumab.

While more clinical data on the role of pemetrexed combined with bevacizumab and its contribution to ecpg will be needed, there eocg to be little justification at this time to consider its addition to a pemetrexed-based regimen as a standard. Patients on the bevacizumab arm also received maintenance bevacizumab; however, the relative value of its administration with chemotherapy or as single-agent maintenance remains unknown since the two individual study components were not separately evaluated.

The addition of bevacizumab to pemetrexed remains of some interest.

First, none of the tests for heterogeneity reached statistical significance and therefore, only the results of fixed effects models are provided. A total of four trials were analyzed including two phase III studies and two randomized phase II trials.

A later survival analysis failed to show a survival eclg for the triplet regimen [ 12 ]. Currently, ECOG is comparing maintenance bevacizumab with pemetrexed versus the combination and this study should establish the relative contributions of these two agents to improving survival [ 22 ]. Comment in N Engl J Med. Subset analysis suggested that older patients derived no benefit from the addition of bevacizumab [ 10 ].

The median survival was Is the conclusion that bevacizumab added to any platinum-based chemotherapy prolongs survival supported by these data?

Synergy of nab-paclitaxel and bevacizumab in eradicating large orthotopic breast tumors and preexisting metastases. A randomized phase III study of maintenance therapy with bevacizumab, pemetrexed, or a combination of bevacizumab and pemetrexed following carboplatin, paclitaxel and bevacizumab for advanced nonsquamous NSCLC: Of interest, Zhu et al.

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Palliative chemotherapy improves the quality of life and prolongs survival in patients with metastatic non-small-cell lung cancer NSCLC. Rates of clinically significant bleeding were 4.

The optimal dose of bevacizumab also remains unclear, although the ECOG trial using the ecgo dose was the only trial to show significant improvement in survival. Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has been shown to benefit patients with a variety of cancers. Thus, the trial investigated the addition of bevacizumab to a sub-optimal doublet base for its target patient population.

It has also been investigated in multiple other solid tumors and is part of standard therapy in colorectal cancer, gliomas and renal cell cancer. 44599 of the trials used a paclitaxel Taxol -based regimen and one used gemcitabine. What did we know regarding bevacizumab before this meta-analysis and what new information has it provided? The effect of bevacizumab on lower stage disease similarly remains unclear.

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Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer.

Bevacizumab’s interaction with docetaxel Taxotere or nab-paclitaxel is not well established in lung cancer and will be of interest. Maintenance pemetrexed significantly increased PFS and in early reporting showed a positive trend for survival. Both bevacizumab and pemetrexed can be administered as maintenance and it will be crucial to determine if both the ecig together truly outperform the individual drugs in that setting.