MAVERICC, a Randomized, Biomarker-stratified, Phase II Study of mFOLFOX6-Bevacizumab versus FOLFIRI-Bevacizumab as First-line Chemotherapy in Metastatic Colorectal Cancer

Background: MAVERICC compared the efficacy and safety of modified leucovorin/5-fluorouracil/oxaliplatin plus bevacizumab (mFOLFOX6-BV) with leucovorin/5-fluorouracil/irinotecan plus BV (FOLFIRI-BV) in patients with previously untreated metastatic colorectal cancer (mCRC). Materials and Methods: MAVERICC was a global, randomized, open-label, phase II study. Primary objectives were to assess associations between 1) excision repair cross-complementing 1 (ERCC1) expression with progression-free survival (PFS), and 2) plasma vascular endothelial growth factor A (VEGF-A) with PFS in patients with previously untreated mCRC receiving mFOLFOX6-BV or FOLFIRI-BV. Before randomization, patients were stratified by tumoral ERCC1/β-actin mRNA expression level and region. Results: Of 376 enrolled patients, 188 each received mFOLFOX6-BV and FOLFIRI-BV. PFS and overall survival (OS) were comparable between FOLFIRI-BV and mFOLFOX6-BV, with numerically higher PFS (HR=0.79; 95% CI: 0.61, 1.01; P=0.06) and OS (HR=0.76; 95% CI: 0.56, 1.04; P=0.09) observed for FOLFIRI-BV. In the high ERCC1 subgroup, PFS and OS were comparable between treatment groups (PFS, HR=0.84; 95% CI: 0.56, 1.26; P=0.40; OS, HR=0.80; 95% CI: 0.51, 1.26; P=0.33). Across treatment groups, high plasma VEGF-A levels (>5.1 pg/mL) were observed with shorter PFS (HR=1.19; 95% CI: 0.93, 1.53; P=0.17) and significantly shorter OS (HR=1.64; 95% CI: 1.20, 2.24; P<0.01) versus low levels (≤5.1 pg/mL). Safety findings for FOLFIRI-BV or mFOLFOX6-BV were comparable to those reported previously. Conclusions: First-line FOLFIRI-BV and mFOLFOX6-BV had comparable PFS and OS, similar to results in patients with high baseline tumor ERCC1 levels. There were no new safety signals with these BV-containing regimens. ClinicalTrials.gov Identifier: NCT01374425