Anti-VEGF and anti-EGFR monoclonal antibodies (Mabs) in the first-line therapy for metastatic colorectal cancer: A meta-analysis

Abstract

e15012 Background: Anti-VEGF (VEGFi) and anti-EGFR (EGFRi) Mabs have increased options for patients with metastatic colorectal cancers (mCRC). The optimal class of antibody to combine with chemotherapy (Ctx) in the first-line treatment for mCRC remains less well defined. Results from randomized controlled trials (RCTs) are variable. Methods: Systematic review and meta-analysis were performed on the basis of previously released RCTs results. We searched the MEDLINE, Cochrane registry, proceedings from ASCO, ECCO, ESMO until 12/ 2008 for RCTs of Mabs in first-line mCRC. Summary statistics were pooled hazard ratio (HR) of progression-free survival (PFS), overall survival (OS) and odds ratio (OR) of Response rate (RR) and 60 day mortality (60d-M). Effect of k-ras wild type and mutation were stratified in trials involving EGFRi. Results: 7 trials with complete data were identified, including 3 Ctx ± VEGFi (AVF2107g, NO16966, JCO2005.05.122), n=2422; 2 Ctx±EGFRi (CRYSTAL, OPUS), n=1554; 2 Ctx/VEGFi ± EGFRi (PACCE, CAIRO-2), n=1789. Addition of VEGFi to Ctx offered 20–30% risk reduction in disease progression and overall mortality, a 30% higher RR and nonsignificant 60d-M. Benefit of EGFRi in addition to Ctx was seen only in k-ras wild type patients with 36% reduction in disease progression and doubling in RR. However, addition of EGFRi to Ctx+VEGFi caused increased risk of progression and death with no significant increase in RR and 60d-M. Conclusions: Benefit of VEGFi in addition to Ctx in first-line mCRC is well pronounced and persistent. In k-ras wild type patients, addition of EGFRi to Ctx results in significant increase in RR and PFS. Addition of EGFRi to Ctx+VEGFi appeared harmful regardless of k- ras status. [Table: see text] [Table: see text]