Gastrointestinal perforation associated with bevacizumab use in metastatic colorectal cancer: Results from a large treatment observational cohort study

Fairooz F. Kabbinavar, Patrick J. Flynn, Mark Kozloff, Mark A. Ashby, Amy Sing, Charles E. Barr, Axel F Grothey

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: Bevacizumab prolongs overall and progression-free survival when added to fluorouracil-based chemotherapy in patients with metastatic colorectal cancer in randomised controlled trials (RCTs). However, gastrointestinal perforation (GIP) occurs in 1-2% of treated patients. We sought to describe the incidence, temporal pattern, outcomes and potential risk factors for GIP in a large, community-based observational cohort study of patients treated with bevacizumab. Patients and methods: Baseline patient and tumour characteristics, including potential GIP risk factors, were collected at study entry. Treatment, targeted adverse events, progression events and survival data were recorded every 3 months. Detailed clinical information was collected for all patients experiencing a GIP event. Effects of baseline risk factors on GIP risk were investigated using Cox proportional hazards regression. Results: Of 1953 evaluable patients followed for a median of 20.1 months, 37 (1.9%) experienced GIP. Most GIP events were surgically managed with successful outcomes; four events were fatal. The majority of GIP events (26/37) occurred ≤6 months after starting bevacizumab (median, 3.35 months). Univariate and multivariate analyses showed that age ≥65 years was significantly associated with lower GIP risk. In multivariate analyses, intact primary tumour and prior adjuvant radiotherapy were significantly associated with increased risk of GIP within 6 months after starting bevacizumab. A regression analysis that assessed the risk of GIP over time showed no cumulative risk associated with bevacizumab exposure. Conclusion: The observed rate of GIP in this large, community-based experience was consistent with rates reported in RCTs. Most events were successfully managed with surgical intervention.

Original languageEnglish (US)
Pages (from-to)1126-1132
Number of pages7
JournalEuropean Journal of Cancer
Volume48
Issue number8
DOIs
StatePublished - May 2012

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Observational Studies
Colorectal Neoplasms
Cohort Studies
Therapeutics
Multivariate Analysis
Randomized Controlled Trials
Adjuvant Radiotherapy
Bevacizumab
Fluorouracil
Disease-Free Survival
Neoplasms
Regression Analysis
Drug Therapy
Survival
Incidence

Keywords

  • Antiangiogenesis
  • Biologics
  • GI perforation
  • Registry
  • Systemic therapy
  • Vascular endothelial growth factor inhibition

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Gastrointestinal perforation associated with bevacizumab use in metastatic colorectal cancer : Results from a large treatment observational cohort study. / Kabbinavar, Fairooz F.; Flynn, Patrick J.; Kozloff, Mark; Ashby, Mark A.; Sing, Amy; Barr, Charles E.; Grothey, Axel F.

In: European Journal of Cancer, Vol. 48, No. 8, 05.2012, p. 1126-1132.

Research output: Contribution to journalArticle

Kabbinavar, Fairooz F. ; Flynn, Patrick J. ; Kozloff, Mark ; Ashby, Mark A. ; Sing, Amy ; Barr, Charles E. ; Grothey, Axel F. / Gastrointestinal perforation associated with bevacizumab use in metastatic colorectal cancer : Results from a large treatment observational cohort study. In: European Journal of Cancer. 2012 ; Vol. 48, No. 8. pp. 1126-1132.
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abstract = "Background: Bevacizumab prolongs overall and progression-free survival when added to fluorouracil-based chemotherapy in patients with metastatic colorectal cancer in randomised controlled trials (RCTs). However, gastrointestinal perforation (GIP) occurs in 1-2{\%} of treated patients. We sought to describe the incidence, temporal pattern, outcomes and potential risk factors for GIP in a large, community-based observational cohort study of patients treated with bevacizumab. Patients and methods: Baseline patient and tumour characteristics, including potential GIP risk factors, were collected at study entry. Treatment, targeted adverse events, progression events and survival data were recorded every 3 months. Detailed clinical information was collected for all patients experiencing a GIP event. Effects of baseline risk factors on GIP risk were investigated using Cox proportional hazards regression. Results: Of 1953 evaluable patients followed for a median of 20.1 months, 37 (1.9{\%}) experienced GIP. Most GIP events were surgically managed with successful outcomes; four events were fatal. The majority of GIP events (26/37) occurred ≤6 months after starting bevacizumab (median, 3.35 months). Univariate and multivariate analyses showed that age ≥65 years was significantly associated with lower GIP risk. In multivariate analyses, intact primary tumour and prior adjuvant radiotherapy were significantly associated with increased risk of GIP within 6 months after starting bevacizumab. A regression analysis that assessed the risk of GIP over time showed no cumulative risk associated with bevacizumab exposure. Conclusion: The observed rate of GIP in this large, community-based experience was consistent with rates reported in RCTs. Most events were successfully managed with surgical intervention.",
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AU - Grothey, Axel F

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AB - Background: Bevacizumab prolongs overall and progression-free survival when added to fluorouracil-based chemotherapy in patients with metastatic colorectal cancer in randomised controlled trials (RCTs). However, gastrointestinal perforation (GIP) occurs in 1-2% of treated patients. We sought to describe the incidence, temporal pattern, outcomes and potential risk factors for GIP in a large, community-based observational cohort study of patients treated with bevacizumab. Patients and methods: Baseline patient and tumour characteristics, including potential GIP risk factors, were collected at study entry. Treatment, targeted adverse events, progression events and survival data were recorded every 3 months. Detailed clinical information was collected for all patients experiencing a GIP event. Effects of baseline risk factors on GIP risk were investigated using Cox proportional hazards regression. Results: Of 1953 evaluable patients followed for a median of 20.1 months, 37 (1.9%) experienced GIP. Most GIP events were surgically managed with successful outcomes; four events were fatal. The majority of GIP events (26/37) occurred ≤6 months after starting bevacizumab (median, 3.35 months). Univariate and multivariate analyses showed that age ≥65 years was significantly associated with lower GIP risk. In multivariate analyses, intact primary tumour and prior adjuvant radiotherapy were significantly associated with increased risk of GIP within 6 months after starting bevacizumab. A regression analysis that assessed the risk of GIP over time showed no cumulative risk associated with bevacizumab exposure. Conclusion: The observed rate of GIP in this large, community-based experience was consistent with rates reported in RCTs. Most events were successfully managed with surgical intervention.

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