Effect of angiotensin system inhibitors on survival in newly diagnosed glioma patients and recurrent glioblastoma patients receiving chemotherapy and/or bevacizumab
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Given prior studies that suggest the use of angiotensin system inhibitors (ASIs) is associated with prolonged overall survival (OS) in glioblastoma (GBM) patients, we evaluated the effect of ASIs in glioma patients receiving chemotherapy and/or bevacizumab (BEV). Using retrospective IRB-approved electronic chart review of newly diagnosed WHO grade 2–4 glioma patients from the Kaiser Permanente Tumor Registry of Northern California, we evaluated the impact of ASIs on OS by Cox proportional hazard model analysis for subgroups who received cytotoxic therapy, cytotoxic therapy with BEV, or BEV alone, as well as those with recurrent GBM (rGBM). Of the 1186 glioma patients who received chemotherapy ASI exposure improved OS (HR 0.82; 95% CI 0.71, 0.93; p = 0.003). When stratified by BEV exposure, a sub-analysis revealed further OS advantage for the BEV group (HR 0.75, 95% CI 0.62, 0.90; p = 0.002). In a second cohort of 181 rGBM patients who received BEV in varying dosages, ASI exposure conferred an OS advantage (HR 0.649; 95% CI 0.46, 0.92; p = 0.016). Moreover, patients with ASI exposure who received low-dose BEV treatment (AUCBEV < 3.6 mg wk/kg) had a significantly longer OS (median = 99 weeks; 95% CI 44.3, 205) than those without ASI (median OS = 55.6 weeks; 95% CI 37.7–73.7; p = 0.032). ASI use is associated with longer OS in glioma patients. Further survival advantage with ASI use was observed in rGBM patients receiving low-dose bevacizumab. These data warrant prospective evaluation of adding ASI to low-dose BEV treatment in GBM patients to improve the outcome of standard therapies.
KeywordsAvastin Bevacizumab Drug dose Angiotensin receptor blockers Glioma Glioblastoma Retrospective analysis
Angiotensin converting enzyme
Angiotensin receptor blocker
Angiotensin II receptor 1
Angiotensin system inhibitor
Central nervous system
Newly diagnosed glioblastoma
Non-small-cell lung cancer
Progression free survival
Renal cell carcinoma
Vascular endothelial growth factor
We thank Dr. D. G. Duda for his scientific input. This study was supported, in part, by NIH- P01CA080124 (to R.K.J.) and NIH-F31HL126449 (to M.D.).
No reagents or funding from these companies were used in these studies.
Compliance with ethical standards
Conflict of interest
V.A.L. received consulting fees from Orbus Therapeutics, Inc., Nativis, Inc., and Bristol-Myers Squibb. R.K.J. received consultant fees from Ophthotech, SPARC, SynDevRx and XTuit. R.K.J owns equity in Enlight, SPARC, SynDevRx and XTuit, and serves on the Board of Directors of XTuit and Boards of Trustees of Tekla Healthcare Investors, Tekla Life Sciences Investors, Tekla Healthcare Opportunities Fund and Tekla World Healthcare Fund. R.K.J only had access to de-identified data.
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