Effect of angiotensin system inhibitors on survival in newly diagnosed glioma patients and recurrent glioblastoma patients receiving chemotherapy and/or bevacizumab

Abstract

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.

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Abbreviations

ACE:

Angiotensin converting enzyme

ARB:

Angiotensin receptor blocker

AT1:

Angiotensin II receptor 1

ASI:

Angiotensin system inhibitor

BEV:

Bevacizumab

CNS:

Central nervous system

GBM:

Glioblastoma

nGBM:

Newly diagnosed glioblastoma

NSCLC:

Non-small-cell lung cancer

OS:

Overall survival

PFS:

Progression free survival

RCC:

Renal cell carcinoma

rGBM:

Recurrent glioblastoma

VEGF:

Vascular endothelial growth factor

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Acknowledgements

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.).

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No reagents or funding from these companies were used in these studies.

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Correspondence to Victor A. Levin.

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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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Levin, V.A., Chan, J., Datta, M. et al. Effect of angiotensin system inhibitors on survival in newly diagnosed glioma patients and recurrent glioblastoma patients receiving chemotherapy and/or bevacizumab. J Neurooncol 134, 325–330 (2017). https://doi.org/10.1007/s11060-017-2528-3

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Keywords

  • Avastin
  • Bevacizumab
  • Drug dose
  • Angiotensin receptor blockers
  • Glioma
  • Glioblastoma
  • Retrospective analysis