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01.05.2014 | Colorectal Cancer | Ausgabe 5/2014 Open Access

Annals of Surgical Oncology 5/2014

Bevacizumab Efficacy in Metastatic Colorectal Cancer is Dependent on Primary Tumor Resection

Annals of Surgical Oncology > Ausgabe 5/2014
MD, PhD Francois Ghiringhelli, PharmD Damien Bichard, PharmD Samuel Limat, MD Veronique Lorgis, MD, PhD Julie Vincent, MD, PhD Christophe Borg, PharmD Julie Berthou, MD David Orry, MD, PhD Pablo Ortega-Deballon, MD Zaher Lakkis, MD, PhD Olivier Facy, MD Bruno Heyd, MD Patrick Rat, PharmD Virginie Nerich, MD, PhD Sylvain Ladoire
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1245/​s10434-013-3463-y) contains supplementary material, which is available to authorized users.



Bevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and second-line metastatic colorectal cancer (mCRC). However, to date, there is no current biomarker predictive for the benefit of bevacizumab use for these patients. Preclinical data suggest that the presence of the primary tumor could be involved in less efficient antitumor activity of antiangiogenic agents, but no clinical data currently support this hypothesis.


We performed a retrospective analysis of factors associated with overall survival (OS) in a study cohort of 409 mCRC patients. Univariate and multivariate Cox proportional hazard regression models were used to assess the influence of primary tumor resection and bevacizumab use on OS. We evaluated associations linking bevacizumab use and OS among patients who previously underwent or did not undergo primary tumor resection. Results were externally validated in a second independent cohort of 328 mCRC patients.


In the study cohort, bevacizumab use and resection of the primary tumor were associated with improved OS. However, subgroup analyses indicate that bevacizumab did not influence survival of patients bearing a primary colorectal tumor (hazard ratio (HR) 0.98, 95 % confidence interval (CI) 0.60–1.61, log-rank test P = 0.6). By contrast, the survival benefit of bevacizumab was restricted to patients who previously underwent primary tumor resection (HR 0.71, 95 % CI 0.55–0.92, P = 0.009). Similar results were observed in the validation cohort.


Addition of bevacizumab to chemotherapy is associated with improvement of OS only in patients with primary tumor resection. These data support the rationale to validate prospectively the influence of primary tumor resection on bevacizumab antitumor effect in synchronous mCRC.

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Supplementary material 1 (EPS 856 kb)
Supplementary material 2 (DOC 93 kb)
Supplementary material 3 (DOC 88 kb)
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Supplementary material 5 (EPS 1148 kb)
Supplementary material 6 (EPS 693 kb)
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