Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab

Frank A. Scappaticci, Jamey R. Skillings, Scott N. Holden, Hans Peter Gerber, Kathy Miller, Fairooz Kabbinavar, Emily Bergsland, James Ngai, Eric Holmgren, Jiuzhou Wang, Herbert Hurwitz

Research output: Contribution to journalArticle

720 Citations (Scopus)

Abstract

Background: Although combination treatment with bevacizumab (humanized monoclonal antibody against vascular endothelial growth factor) and chemotherapy improves survival of patients with various metastatic carcinomas, an increased risk of arterial thromboembolic events has been observed in some trials. We characterized this risk by performing post hoc analyses of randomized controlled trials that evaluated combination treatment with bevacizumab and chemotherapy versus chemotherapy alone. Low-dose aspirin was permitted in these trials, and its safety was also analyzed. Methods: Data were pooled from five randomized controlled trials that included a total of 1745 patients with metastatic colorectal, breast, or non-small-cell lung carcinoma. The risk of an arterial or venous thromboembolic event was assessed by simple incidence rates, rates per 100 person-years, and/or hazard ratios (HRs). The association between patient characteristics and risk of an arterial thromboembolic event was investigated primarily by Cox proportional hazards regression. The relationship between low-dose aspirin and bleeding was explored by incidence rates and rates per 100 person-years. Results: Combined treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with increased risk for an arterial thromboembolic event (HR = 2.0, 95% confidence interval [CI] = 1.05 to 3.75; P = .031) but not for a venous thromboembolic event (HR = 0.89, 95% CI = 0.66 to 1.20; P = .44). The absolute rate of developing an arterial thromboembolism was 5.5 events per 100 person-years for those receiving combination therapy and 3.1 events per 100 person-years for those receiving chemotherapy alone (ratio = 1.8, 95% CI = 0.94 to 3.33; P = .076). Development of an arterial thromboembolic event was associated with a prior arterial thromboembolic event (P<.001) or age of 65 years or older (P = .01). Baseline or on-study aspirin use was associated with modest increases in grade 3 and 4 bleeding events in both treatment groups, from 3.6% to 4.7% for bevacizumab-treated patients and from 1.7% to 2.2% for control subjects. Conclusions: Combination treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with an increased risk of arterial thromboembolism but not venous thromboembolism.

Original languageEnglish
Pages (from-to)1232-1239
Number of pages8
JournalJournal of the National Cancer Institute
Volume99
Issue number16
DOIs
StatePublished - Aug 15 2007

Fingerprint

Carcinoma
Drug Therapy
Aspirin
Thromboembolism
Confidence Intervals
Therapeutics
Randomized Controlled Trials
Hemorrhage
Antibodies, Monoclonal, Humanized
Bevacizumab
Incidence
Venous Thromboembolism
Non-Small Cell Lung Carcinoma
Vascular Endothelial Growth Factor A
Breast
Safety
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. / Scappaticci, Frank A.; Skillings, Jamey R.; Holden, Scott N.; Gerber, Hans Peter; Miller, Kathy; Kabbinavar, Fairooz; Bergsland, Emily; Ngai, James; Holmgren, Eric; Wang, Jiuzhou; Hurwitz, Herbert.

In: Journal of the National Cancer Institute, Vol. 99, No. 16, 15.08.2007, p. 1232-1239.

Research output: Contribution to journalArticle

Scappaticci, FA, Skillings, JR, Holden, SN, Gerber, HP, Miller, K, Kabbinavar, F, Bergsland, E, Ngai, J, Holmgren, E, Wang, J & Hurwitz, H 2007, 'Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab', Journal of the National Cancer Institute, vol. 99, no. 16, pp. 1232-1239. https://doi.org/10.1093/jnci/djm086
Scappaticci, Frank A. ; Skillings, Jamey R. ; Holden, Scott N. ; Gerber, Hans Peter ; Miller, Kathy ; Kabbinavar, Fairooz ; Bergsland, Emily ; Ngai, James ; Holmgren, Eric ; Wang, Jiuzhou ; Hurwitz, Herbert. / Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. In: Journal of the National Cancer Institute. 2007 ; Vol. 99, No. 16. pp. 1232-1239.
@article{d2045feb6ad745dca56a4fb63b2e7c6e,
title = "Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab",
abstract = "Background: Although combination treatment with bevacizumab (humanized monoclonal antibody against vascular endothelial growth factor) and chemotherapy improves survival of patients with various metastatic carcinomas, an increased risk of arterial thromboembolic events has been observed in some trials. We characterized this risk by performing post hoc analyses of randomized controlled trials that evaluated combination treatment with bevacizumab and chemotherapy versus chemotherapy alone. Low-dose aspirin was permitted in these trials, and its safety was also analyzed. Methods: Data were pooled from five randomized controlled trials that included a total of 1745 patients with metastatic colorectal, breast, or non-small-cell lung carcinoma. The risk of an arterial or venous thromboembolic event was assessed by simple incidence rates, rates per 100 person-years, and/or hazard ratios (HRs). The association between patient characteristics and risk of an arterial thromboembolic event was investigated primarily by Cox proportional hazards regression. The relationship between low-dose aspirin and bleeding was explored by incidence rates and rates per 100 person-years. Results: Combined treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with increased risk for an arterial thromboembolic event (HR = 2.0, 95{\%} confidence interval [CI] = 1.05 to 3.75; P = .031) but not for a venous thromboembolic event (HR = 0.89, 95{\%} CI = 0.66 to 1.20; P = .44). The absolute rate of developing an arterial thromboembolism was 5.5 events per 100 person-years for those receiving combination therapy and 3.1 events per 100 person-years for those receiving chemotherapy alone (ratio = 1.8, 95{\%} CI = 0.94 to 3.33; P = .076). Development of an arterial thromboembolic event was associated with a prior arterial thromboembolic event (P<.001) or age of 65 years or older (P = .01). Baseline or on-study aspirin use was associated with modest increases in grade 3 and 4 bleeding events in both treatment groups, from 3.6{\%} to 4.7{\%} for bevacizumab-treated patients and from 1.7{\%} to 2.2{\%} for control subjects. Conclusions: Combination treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with an increased risk of arterial thromboembolism but not venous thromboembolism.",
author = "Scappaticci, {Frank A.} and Skillings, {Jamey R.} and Holden, {Scott N.} and Gerber, {Hans Peter} and Kathy Miller and Fairooz Kabbinavar and Emily Bergsland and James Ngai and Eric Holmgren and Jiuzhou Wang and Herbert Hurwitz",
year = "2007",
month = "8",
day = "15",
doi = "10.1093/jnci/djm086",
language = "English",
volume = "99",
pages = "1232--1239",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "16",

}

TY - JOUR

T1 - Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab

AU - Scappaticci, Frank A.

AU - Skillings, Jamey R.

AU - Holden, Scott N.

AU - Gerber, Hans Peter

AU - Miller, Kathy

AU - Kabbinavar, Fairooz

AU - Bergsland, Emily

AU - Ngai, James

AU - Holmgren, Eric

AU - Wang, Jiuzhou

AU - Hurwitz, Herbert

PY - 2007/8/15

Y1 - 2007/8/15

N2 - Background: Although combination treatment with bevacizumab (humanized monoclonal antibody against vascular endothelial growth factor) and chemotherapy improves survival of patients with various metastatic carcinomas, an increased risk of arterial thromboembolic events has been observed in some trials. We characterized this risk by performing post hoc analyses of randomized controlled trials that evaluated combination treatment with bevacizumab and chemotherapy versus chemotherapy alone. Low-dose aspirin was permitted in these trials, and its safety was also analyzed. Methods: Data were pooled from five randomized controlled trials that included a total of 1745 patients with metastatic colorectal, breast, or non-small-cell lung carcinoma. The risk of an arterial or venous thromboembolic event was assessed by simple incidence rates, rates per 100 person-years, and/or hazard ratios (HRs). The association between patient characteristics and risk of an arterial thromboembolic event was investigated primarily by Cox proportional hazards regression. The relationship between low-dose aspirin and bleeding was explored by incidence rates and rates per 100 person-years. Results: Combined treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with increased risk for an arterial thromboembolic event (HR = 2.0, 95% confidence interval [CI] = 1.05 to 3.75; P = .031) but not for a venous thromboembolic event (HR = 0.89, 95% CI = 0.66 to 1.20; P = .44). The absolute rate of developing an arterial thromboembolism was 5.5 events per 100 person-years for those receiving combination therapy and 3.1 events per 100 person-years for those receiving chemotherapy alone (ratio = 1.8, 95% CI = 0.94 to 3.33; P = .076). Development of an arterial thromboembolic event was associated with a prior arterial thromboembolic event (P<.001) or age of 65 years or older (P = .01). Baseline or on-study aspirin use was associated with modest increases in grade 3 and 4 bleeding events in both treatment groups, from 3.6% to 4.7% for bevacizumab-treated patients and from 1.7% to 2.2% for control subjects. Conclusions: Combination treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with an increased risk of arterial thromboembolism but not venous thromboembolism.

AB - Background: Although combination treatment with bevacizumab (humanized monoclonal antibody against vascular endothelial growth factor) and chemotherapy improves survival of patients with various metastatic carcinomas, an increased risk of arterial thromboembolic events has been observed in some trials. We characterized this risk by performing post hoc analyses of randomized controlled trials that evaluated combination treatment with bevacizumab and chemotherapy versus chemotherapy alone. Low-dose aspirin was permitted in these trials, and its safety was also analyzed. Methods: Data were pooled from five randomized controlled trials that included a total of 1745 patients with metastatic colorectal, breast, or non-small-cell lung carcinoma. The risk of an arterial or venous thromboembolic event was assessed by simple incidence rates, rates per 100 person-years, and/or hazard ratios (HRs). The association between patient characteristics and risk of an arterial thromboembolic event was investigated primarily by Cox proportional hazards regression. The relationship between low-dose aspirin and bleeding was explored by incidence rates and rates per 100 person-years. Results: Combined treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with increased risk for an arterial thromboembolic event (HR = 2.0, 95% confidence interval [CI] = 1.05 to 3.75; P = .031) but not for a venous thromboembolic event (HR = 0.89, 95% CI = 0.66 to 1.20; P = .44). The absolute rate of developing an arterial thromboembolism was 5.5 events per 100 person-years for those receiving combination therapy and 3.1 events per 100 person-years for those receiving chemotherapy alone (ratio = 1.8, 95% CI = 0.94 to 3.33; P = .076). Development of an arterial thromboembolic event was associated with a prior arterial thromboembolic event (P<.001) or age of 65 years or older (P = .01). Baseline or on-study aspirin use was associated with modest increases in grade 3 and 4 bleeding events in both treatment groups, from 3.6% to 4.7% for bevacizumab-treated patients and from 1.7% to 2.2% for control subjects. Conclusions: Combination treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with an increased risk of arterial thromboembolism but not venous thromboembolism.

UR - http://www.scopus.com/inward/record.url?scp=34548141828&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548141828&partnerID=8YFLogxK

U2 - 10.1093/jnci/djm086

DO - 10.1093/jnci/djm086

M3 - Article

C2 - 17686822

AN - SCOPUS:34548141828

VL - 99

SP - 1232

EP - 1239

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 16

ER -