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Clinical Trial
. 2015 Feb 3;112(5):1547-52.
doi: 10.1073/pnas.1424024112. Epub 2015 Jan 20.

VSports在线直播 - Improved tumor vascularization after anti-VEGF therapy with carboplatin and nab-paclitaxel associates with survival in lung cancer

Affiliations
Clinical Trial

Improved tumor vascularization after anti-VEGF therapy with carboplatin and nab-paclitaxel associates with survival in lung cancer

VSports注册入口 - Rebecca S Heist et al. Proc Natl Acad Sci U S A. .

Abstract

Addition of anti-VEGF antibody therapy to standard chemotherapies has improved survival and is an accepted standard of care for advanced non-small cell lung cancer (NSCLC). However, the mechanisms by which anti-VEGF therapy increases survival remain unclear. We evaluated dynamic CT-based vascular parameters and plasma cytokines after bevacizumab alone and after bevacizumab plus chemotherapy with carboplatin and nab-paclitaxel in advanced NSCLC patients to explore potential biomarkers of treatment response and resistance to this regimen. Thirty-six patients were enrolled in this study. The primary end point was 6-mo progression-free survival rate, which was 74% (95% CI: 57, 97). This regimen has a promising overall response rate of 36% and median time to progression of 8. 5 (6. 0, 38. 7) mo and overall survival of 12 VSports手机版. 2 (9. 6, 44. 1) mo. We found that anti-VEGF therapy led to a sustained increase in plasma PlGF, a potential pharmacodynamic marker. We also found that higher levels of soluble VEGFR1 measured before starting bevacizumab with chemotherapy were associated with worse survival, supporting its potential role as biomarker of treatment resistance. Our imaging biomarker studies indicate that bevacizumab-based treatment-while reducing blood flow, volume, and permeability in the overall population-may be associated with improved survival in patients with improved tumor vasculature and blood perfusion after treatment. This hypothesis-generating study supports the notion that excessively decreasing vascular permeability and pruning/rarefaction after bevacizumab therapy may negatively impact the outcome of combination therapy in NSCLC patients. This hypothesis warrants further dose-titration studies of bevacizumab to examine the dose effect on tumor vasculature and treatment efficacy. .

Keywords: antiangiogenesis; bioimaging; lung cancer V体育安卓版. .

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Conflict of interest statement

Conflict of interest statement: R. S. H. has served as a consultant for Boehringer-Ingelheim and Momenta. D V体育ios版. G. D. has served as a consultant for Hexal/Sandoz. P. F. has served on the speakers’ bureau for Boehringer-Ingelheim and Genentech/Roche, and on an advisory board for Boehringer-Ingelheim and Genentech/Roche. L. V. S. has served as a consultant (uncompensated) for Clovis, Astrazeneca, Boehringer Ingelheim, Genentech/Roche, Novartis, Merrimack, and Taiho. J. S. T. received travel funds from Helsinn Therapeutics. A. T. S. has served as a consultant for Pfizer, Novartis, Ariad, Chugai, Ignyta, Genentech/Roche, and Daiichi-Sankyo. L. G. has served as a consultant for Merck and on an advisory board for Merck and Genentech/Roche. N. A. P. has served as a consultant for Genentech. J. W. N. has served as a consultant for Clovis. T. J. L. has served on the board of directors for BMS, on a scientific advisory board for Arvinas, and has an EGFR mutation-testing patent from Partners Healthcare. J. A. E. has received consulting fees from Genentech, Roche, Ventana, and Chugai, and is coinventor on a patent licensed by Ventana. R. K. J. has received research grants from MedImmune and Roche for research unrelated to this study; has received consultant fees from Enlight, Ophthotech, and SynDevRx; owns equity in Enlight, Ophthotech, SynDevRx, and XTuit; and serves on the Board of Directors of XTuit and Boards of Trustees of Tekla Healthcare Investors, Tekla Life Sciences Investors, and Tekla Healthcare Opportunities Fund. Funding for the clinical trial was provided by Celgene and Roche/Genentech, which provided study drugs and funding for the clinical trial. All data collection and analysis were performed independently by the investigators of this investigator-initiated clinical trial.

"VSports手机版" Figures

Fig. 1.
Fig. 1.
Survival outcomes after bevacizumab alone followed by combination of bevacizumab with chemotherapy in NSCLC patients. Kaplan–Meier distributions for PFS (A) and OS (B).
Fig. 2.
Fig. 2.
Association between changes in functional vascular parameters after bevacizumab alone and after bevacizumab with chemotherapy and overall survival in NSCLC patients. (A) Kaplan–Meier OS distributions for changes in MTT during combination therapy. Note the favorable OS in the tertiles with low ΔMTT values. (B) Kaplan–Meier OS distributions for changes in P-S product after bevacizumab alone and before combination therapy. Note the poor OS in the tertiles with low ΔP-S values.

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References

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