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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Is the conclusion that bevacizumab added to any platinum-based chemotherapy prolongs survival supported by these data? A total of four trials were analyzed including two phase III studies and two randomized phase II trials. Similarly, motesanib did not significantly improve survival [ 27 ]. Anti-angiogenic therapy continues to hold promise and clearly benefits some patients. We do not believe so and consider an evidence-based survival benefit to be limited to paclitaxel and carboplatin.
First, none of the tests for heterogeneity reached statistical significance and therefore, only the results of fixed effects models are provided.
All the remaining authors have declared no conflicts of interest. Outcomes for elderly, advanced-stage non-small-cell lung cancer patients treated with bevacizumab in 45999 with carboplatin and paclitaxel: Two randomized phase II studies are also included in the meta-analysis and evaluated bevacizumab added to paclitaxel [ 1314 ].
Comment in N Engl J Med. In luciferase-tagged breast cancer mouse models with metastases to lungs, metastasis formation was decreased with nab-paclitaxel and bevacizumab when compared with each drug alone [ 21 ].
Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer.
Bevacizumab remains of interest in the adjuvant setting as currently investigated in ECOG 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.
Attempts to increase the activity of chemotherapy in a non-selective manner dcog included the addition of monoclonal antibodies, in particular, antibodies directed against the epidermal growth factor receptor EGFR or against the vascular endothelial growth factor VEGF. What are some of the current questions of interest regarding bevacizumab?
Vandetanib plus pemetrexed for the second-line treatment of advanced non-small-cell lung cancer: Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: Rates of clinically significant bleeding were 4.
Of interest, Zhu et al. The optimal dose of bevacizumab also remains unclear, although the ECOG trial using the higher dose was the only trial to show significant improvement in survival. They also conclude that bevacizumab showed greater efficacy in patients with adenocarcinoma, and lower body weight loss, but detected no apparent interaction of the treatment effect with age.
Doublet platinum-based chemotherapy has been accepted evidence-based therapy for the last two decades. The overall marginally positive statistical survival data reported by the authors are most likely explained by the fact that the large paclitaxel-based trial ECOG is not fundamentally disturbed by the less positive gemcitabine trial AVAiLwhile the two smaller paclitaxel-based studies contribute only marginally to the overall results.
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. Gemcitabine plus bevacizumab compared rcog gemcitabine plus placebo in patients with advanced pancreatic cancer: Recent modifications have been the introduction of histology as a parameter defining ecg optimal choice of a doublet regimen and the emergence of single-agent maintenance chemotherapy for patients without progression on initial doublet therapy [ 12 ].
Between July and Aprilthe Eastern 45999 Oncology Group ECOG conducted a randomized study in which patients with recurrent or advanced non-small-cell lung cancer stage IIIB or IV were assigned to chemotherapy with paclitaxel and carboplatin alone or paclitaxel and carboplatin plus bevacizumab Maintenance pemetrexed significantly increased PFS and in early reporting showed a positive trend for survival.
A later survival analysis failed to show a survival benefit for the triplet regimen [ 12 ].
Phase III study of carboplatin and paclitaxel alone or with sorafinib in advanced non-small-cell lung cancer. Overall survival with cisplatin—gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: Prognostic significance of angiogenesis and angiogenic growth factors in nonsmall cell lung cancer. The primary end point ecoh overall survival.
In this meta-analysis, diminished activity of bevacizumab in older patients was not seen, while the single-trial sub-analysis of ECOG suggested no benefit for older patients. 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.
Thus, the trial eckg the addition of bevacizumab to a sub-optimal doublet base for its target patient population. While more clinical data on the role of pemetrexed combined with bevacizumab and its contribution to maintenance will be needed, there appears to be little justification at this time to consider its addition to a pemetrexed-based regimen as a standard.
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. Analyzed separately, these trials support the administration of bevacizumab with carboplatin and paclitaxel, while its administration with gemcitabine underperforms for the survival end point and is not clinically relevant since gemcitabine is preferentially given to patients with squamous cell histology who are poor candidates for bevacizumab due to risk of pulmonary hemorrhage.
Palliative chemotherapy improves the quality of life and prolongs survival in patients with metastatic non-small-cell lung cancer NSCLC. Bevacizumab’s interaction with docetaxel Taxotere or nab-paclitaxel is not well established in lung cancer and will be of interest. Does bevacizumab selectively enhance paclitaxel-based regimens?
There were 15 treatment-related deaths in the chemotherapy-plus-bevacizumab group, including 5 from pulmonary hemorrhage. When attempting to integrate bevacizumab with radiation complications included tracheoesophageal fistula with fatal hemoptysis and this approach is not being pursued. In that case, the doublet would likely be more tolerable and cost-effective. Disclosure — in the Blink of an Eye.
The broad conclusion that bevacizumab can edog added to doublet chemotherapy with 5499 survival benefit seems exaggerated, given that only eocg specific doublets were examined, one in patients who would no longer be offered the drug i. It has also been investigated in multiple other solid tumors and is part of standard therapy in colorectal cancer, gliomas and renal cell cancer.
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Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer.
However, a majority of patients 459 not have this option and continue to be offered standard doublet chemotherapy.
A study of docetaxel with or without vandetanib showed a PFS benefit, whereas there was no significant difference in PFS with pemetrexed [ 2324 ].
The authors conclude that bevacizumab prolongs survival when added to first-line platinum-based chemotherapy overall HR 0.
In the phase III AVAiL trial, patients were treated with cisplatin and gemcitabine versus the triplet regimen with bevacizumab administered at either 7.
Receive exclusive offers and updates from Oxford Academic. Weekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma. The median progression-free survival in the two groups was 6. 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 ].