Magnitude of benefit of the addition of bevacizumab to first-line chemotherapy for metastatic colorectal cancer: meta-analysis of randomized clinical trials View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-12

AUTHORS

Fotios Loupakis, Emilio Bria, Vanja Vaccaro, Federica Cuppone, Michele Milella, Paolo Carlini, Chiara Cremolini, Lisa Salvatore, Alfredo Falcone, Paola Muti, Isabella Sperduti, Diana Giannarelli, Francesco Cognetti

ABSTRACT

BACKGROUND: Although the addition of bevacizumab to 1st line chemotherapy provides a significant survival benefit for advanced colorectal cancer, the magnitudes of both advantages and toxicities have not been extensively investigated. METHODS: A literature-based meta-analysis was conducted; Hazard Ratios were extracted from randomized trials for primary end-points (Progression Free Survival, PFS, Overall Survival OS). The log of event-based risk ratio were derived for secondary endpoints (objective/partial response rate, ORR/PR; severe hypertension, bleeding and proteinuria). Absolute differences and the number needed to treat/harm (NNT/NNH) were calculated. A meta-regression analysis with clinical predictors and a sensitivity analysis according to the trial phase-design were conducted as well. RESULTS: Five trials (2,728 pts) were selected. The addition of bevacizumab to 1st line chemotherapy significantly increased both PFS (although with significant heterogeneity) and OS over exclusive chemotherapy by 17.1% and 8.6% (NNT 6 and 12), regardless of the study setting (non significant interaction between phase II and III). The chance to improve PR was significantly increased by 6.5% (NNT 15), with a trend for ORR. The risk of hypertension was significantly increased by 6.2% (NNH 16). According to the meta-regression analysis, female gender and rectal primary site were significant predictors for PFS benefit. CONCLUSIONS: Notwithstanding all the concerns related to costs and the significant HTN risk, the significant outcome improvement provided by bevacizumab in first-line treatment for unselected advanced colorectal cancer patients, should be considered when choosing the appropriate up-front therapy. More... »

PAGES

58

References to SciGraph publications

  • 2005-12. Angiogenesis as a therapeutic target in NATURE
  • 2009-12. Targeting targeted agents: open issues for clinical trial design in JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/1756-9966-29-58

    DOI

    http://dx.doi.org/10.1186/1756-9966-29-58

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1039017238

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20504361


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