title: Bevacizumab Efficacy Is Influenced by Primary Tumor Resection in First-Line Treatment of Metastatic Colorectal Cancer in a Retrospective Multicenter Study.
abstract: There is no predictive factor of response to bevacizumab in metastatic colorectal cancer. Nevertheless, preclinical studies demonstrated an interaction between primary tumor and metastatic sites for the neoangiogenesis regulation. The primary objective of our study was to identify an effect of up-front primary tumor resection (UPTR) on bevacizumab efficacy.
  
  
  
  Between 2008 and 2010, we retrospectively analyzed progression-free survival (PFS) and overall survival (OS) of 316 patients with synchronous and metachronous metastatic colorectal cancer according to bevacizumab addition to first-line chemotherapy and UPTR.
  
  
  
  Among 206 patients with UPTR, the addition of bevacizumab to chemotherapy significantly improved OS compared to chemotherapy alone (29.8 vs. 23.9 months respectively; hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.40-0.83; P = .003). This effect was confirmed in multivariate analysis. There was also a nonsignificant trend toward improved PFS (9.7 vs. 8.4 months respectively; HR 0.71; 95% CI, 0.50-1.02; P = .062). Conversely, among 110 patients without UPTR, the addition of bevacizumab to chemotherapy had no effect on OS compared to chemotherapy alone (18.2 vs. 19.3 months respectively; HR 0.96; 95% CI, 0.65-1.42; P = .853). Bevacizumab significantly improved PFS (8.1 vs. 5.7 months respectively; HR 0.66; 95% CI, 0.45-0.96; P = .032) without confirmation in multivariate analysis.
  
  
  
  In this retrospective study, bevacizumab seems to improve OS only in patients with UPTR, which could suggest a complementarity of both therapeutic modalities for antiangiogenic effect.
authors.affiliation: Institut de Cancérologie de l'Ouest (ICO) René Gauducheau, Saint-Herblain, France. Electronic address: mathilde.cabart@ico.unicancer.fr.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Cabart
authors.affiliation: Institut de Cancérologie de l'Ouest (ICO) René Gauducheau, Saint-Herblain, France.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Frénel
authors.affiliation: Institut de Cancérologie de l'Ouest (ICO) René Gauducheau, Saint-Herblain, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Campion
authors.affiliation: Centre Catherine de Sienne, Nantes, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Ramée
authors.affiliation: Centre Jean Bernard, Le Mans, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Dupuis
authors.affiliation: Institut de Cancérologie de l'Ouest (ICO) René Gauducheau, Saint-Herblain, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Senellart
authors.affiliation: Institut de Cancérologie de l'Ouest (ICO) René Gauducheau, Saint-Herblain, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Hiret
authors.affiliation: Institut de Cancérologie de l'Ouest (ICO) René Gauducheau, Saint-Herblain, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
authors.affiliation: Institut de Cancérologie de l'Ouest (ICO) René Gauducheau, Saint-Herblain, France.
authors.forename: Jaafar
authors.initials: J
authors.lastname: Bennouna
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab
keywords: Angiogenesis; First-line chemotherapy; Metastasis; Surgery