Treatment-related mortality with vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy in patients with advanced solid tumors: A meta-analysis

Shanthi Sivendran, Ziyue Liu, Louis J. Portas, Menggang Yu, Noah Hahn, Guru Sonpavde, William K. Oh, Matthew D. Galsky

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Background: Several vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKI) are now approved by regulatory agencies and are important in the treatment of solid tumor malignancies. The risk of fatal adverse events (FAEs) with these agents is not well characterized. Methods: PubMed was searched for articles published from 2001 until 2011. Eligible studies included prospective randomized trials evaluating sunitinib, sorafenib, pazopanib, and vandetanib in patients with all malignancies. Thirteen eligible randomized controlled trials were included in a meta-analysis and the number of FAEs (defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) criteria) was extracted and study quality was calculated. Incidence rates and relative risks were calculated for all thirteen studies as well as for the subset of patients with renal cell carcinoma. Results: Analysis of the 5164 patients across 13 RCTs revealed that the relative risk was 1.64 (95% CI, 1.16, 2.32; P= 0.01; incidence 2.26% vs. 1.26%) for the association of a VEGFR TKI with FAEs using a random-effects model. All exploratory subgroup analyses indicated a trend toward an increase risk of FAEs with VEGFR TKI treatment, though the subgroup analyses reached statistical significance for renal carcinoma studies, studies utilizing placebo as the control arm, and studies evaluating sorafenib. Interpretation: This analysis suggests that VEGFR TKIs are associated with a significant increase in the risk of FAEs in patients with advanced solid tumors.

Original languageEnglish
Pages (from-to)919-925
Number of pages7
JournalCancer Treatment Reviews
Volume38
Issue number7
DOIs
StatePublished - Nov 2012

Fingerprint

Vascular Endothelial Growth Factor Receptor
Protein-Tyrosine Kinases
Meta-Analysis
Mortality
Neoplasms
Therapeutics
National Cancer Institute (U.S.)
Incidence
Renal Cell Carcinoma
PubMed
Terminology
Randomized Controlled Trials
Placebos
Prospective Studies
Carcinoma
Kidney

Keywords

  • Cancer
  • Fatal adverse events
  • Meta-analysis
  • Mortality
  • Pazopanib
  • Renal cell cancer
  • Sorafenib
  • Sunitinib
  • Vandetanib
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Treatment-related mortality with vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy in patients with advanced solid tumors : A meta-analysis. / Sivendran, Shanthi; Liu, Ziyue; Portas, Louis J.; Yu, Menggang; Hahn, Noah; Sonpavde, Guru; Oh, William K.; Galsky, Matthew D.

In: Cancer Treatment Reviews, Vol. 38, No. 7, 11.2012, p. 919-925.

Research output: Contribution to journalArticle

Sivendran, Shanthi ; Liu, Ziyue ; Portas, Louis J. ; Yu, Menggang ; Hahn, Noah ; Sonpavde, Guru ; Oh, William K. ; Galsky, Matthew D. / Treatment-related mortality with vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy in patients with advanced solid tumors : A meta-analysis. In: Cancer Treatment Reviews. 2012 ; Vol. 38, No. 7. pp. 919-925.
@article{c334188f77a74bacb33e41ee88895592,
title = "Treatment-related mortality with vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy in patients with advanced solid tumors: A meta-analysis",
abstract = "Background: Several vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKI) are now approved by regulatory agencies and are important in the treatment of solid tumor malignancies. The risk of fatal adverse events (FAEs) with these agents is not well characterized. Methods: PubMed was searched for articles published from 2001 until 2011. Eligible studies included prospective randomized trials evaluating sunitinib, sorafenib, pazopanib, and vandetanib in patients with all malignancies. Thirteen eligible randomized controlled trials were included in a meta-analysis and the number of FAEs (defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) criteria) was extracted and study quality was calculated. Incidence rates and relative risks were calculated for all thirteen studies as well as for the subset of patients with renal cell carcinoma. Results: Analysis of the 5164 patients across 13 RCTs revealed that the relative risk was 1.64 (95{\%} CI, 1.16, 2.32; P= 0.01; incidence 2.26{\%} vs. 1.26{\%}) for the association of a VEGFR TKI with FAEs using a random-effects model. All exploratory subgroup analyses indicated a trend toward an increase risk of FAEs with VEGFR TKI treatment, though the subgroup analyses reached statistical significance for renal carcinoma studies, studies utilizing placebo as the control arm, and studies evaluating sorafenib. Interpretation: This analysis suggests that VEGFR TKIs are associated with a significant increase in the risk of FAEs in patients with advanced solid tumors.",
keywords = "Cancer, Fatal adverse events, Meta-analysis, Mortality, Pazopanib, Renal cell cancer, Sorafenib, Sunitinib, Vandetanib, Vascular endothelial growth factor",
author = "Shanthi Sivendran and Ziyue Liu and Portas, {Louis J.} and Menggang Yu and Noah Hahn and Guru Sonpavde and Oh, {William K.} and Galsky, {Matthew D.}",
year = "2012",
month = "11",
doi = "10.1016/j.ctrv.2012.05.001",
language = "English",
volume = "38",
pages = "919--925",
journal = "Cancer Treatment Reviews",
issn = "0305-7372",
publisher = "W.B. Saunders Ltd",
number = "7",

}

TY - JOUR

T1 - Treatment-related mortality with vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy in patients with advanced solid tumors

T2 - A meta-analysis

AU - Sivendran, Shanthi

AU - Liu, Ziyue

AU - Portas, Louis J.

AU - Yu, Menggang

AU - Hahn, Noah

AU - Sonpavde, Guru

AU - Oh, William K.

AU - Galsky, Matthew D.

PY - 2012/11

Y1 - 2012/11

N2 - Background: Several vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKI) are now approved by regulatory agencies and are important in the treatment of solid tumor malignancies. The risk of fatal adverse events (FAEs) with these agents is not well characterized. Methods: PubMed was searched for articles published from 2001 until 2011. Eligible studies included prospective randomized trials evaluating sunitinib, sorafenib, pazopanib, and vandetanib in patients with all malignancies. Thirteen eligible randomized controlled trials were included in a meta-analysis and the number of FAEs (defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) criteria) was extracted and study quality was calculated. Incidence rates and relative risks were calculated for all thirteen studies as well as for the subset of patients with renal cell carcinoma. Results: Analysis of the 5164 patients across 13 RCTs revealed that the relative risk was 1.64 (95% CI, 1.16, 2.32; P= 0.01; incidence 2.26% vs. 1.26%) for the association of a VEGFR TKI with FAEs using a random-effects model. All exploratory subgroup analyses indicated a trend toward an increase risk of FAEs with VEGFR TKI treatment, though the subgroup analyses reached statistical significance for renal carcinoma studies, studies utilizing placebo as the control arm, and studies evaluating sorafenib. Interpretation: This analysis suggests that VEGFR TKIs are associated with a significant increase in the risk of FAEs in patients with advanced solid tumors.

AB - Background: Several vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKI) are now approved by regulatory agencies and are important in the treatment of solid tumor malignancies. The risk of fatal adverse events (FAEs) with these agents is not well characterized. Methods: PubMed was searched for articles published from 2001 until 2011. Eligible studies included prospective randomized trials evaluating sunitinib, sorafenib, pazopanib, and vandetanib in patients with all malignancies. Thirteen eligible randomized controlled trials were included in a meta-analysis and the number of FAEs (defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) criteria) was extracted and study quality was calculated. Incidence rates and relative risks were calculated for all thirteen studies as well as for the subset of patients with renal cell carcinoma. Results: Analysis of the 5164 patients across 13 RCTs revealed that the relative risk was 1.64 (95% CI, 1.16, 2.32; P= 0.01; incidence 2.26% vs. 1.26%) for the association of a VEGFR TKI with FAEs using a random-effects model. All exploratory subgroup analyses indicated a trend toward an increase risk of FAEs with VEGFR TKI treatment, though the subgroup analyses reached statistical significance for renal carcinoma studies, studies utilizing placebo as the control arm, and studies evaluating sorafenib. Interpretation: This analysis suggests that VEGFR TKIs are associated with a significant increase in the risk of FAEs in patients with advanced solid tumors.

KW - Cancer

KW - Fatal adverse events

KW - Meta-analysis

KW - Mortality

KW - Pazopanib

KW - Renal cell cancer

KW - Sorafenib

KW - Sunitinib

KW - Vandetanib

KW - Vascular endothelial growth factor

UR - http://www.scopus.com/inward/record.url?scp=84865439183&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84865439183&partnerID=8YFLogxK

U2 - 10.1016/j.ctrv.2012.05.001

DO - 10.1016/j.ctrv.2012.05.001

M3 - Article

C2 - 22651902

AN - SCOPUS:84865439183

VL - 38

SP - 919

EP - 925

JO - Cancer Treatment Reviews

JF - Cancer Treatment Reviews

SN - 0305-7372

IS - 7

ER -