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.
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 cancerpatients, should be considered when choosing the appropriate up-front therapy.
Authors: Fairooz F Kabbinavar; Julie Hambleton; Robert D Mass; Herbert I Hurwitz; Emily Bergsland; Somnath Sarkar Journal: J Clin Oncol Date: 2005-05-02 Impact factor: 44.544
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Authors: Fairooz Kabbinavar; Herbert I Hurwitz; Louis Fehrenbacher; Neal J Meropol; William F Novotny; Grazyna Lieberman; Susan Griffing; Emily Bergsland Journal: J Clin Oncol Date: 2003-01-01 Impact factor: 44.544
Authors: Herbert I Hurwitz; Niall C Tebbutt; Fairooz Kabbinavar; Bruce J Giantonio; Zhong-Zhen Guan; Lada Mitchell; Daniel Waterkamp; Josep Tabernero Journal: Oncologist Date: 2013-07-23
Authors: Sara Mariucci; Bianca Rovati; Mariangela Manzoni; Matteo Giovanni Della Porta; Giuditta Comolli; Sara Delfanti; Marco Danova Journal: Clin Exp Med Date: 2010-12-16 Impact factor: 3.984
Authors: F Loupakis; M Schirripa; C Caparello; N Funel; L Pollina; E Vasile; C Cremolini; L Salvatore; M Morvillo; C Antoniotti; F Marmorino; G Masi; A Falcone Journal: Br J Cancer Date: 2013-05-23 Impact factor: 7.640