MAVERICC, a phase 2 study of mFOLFOX6-bevacizumab (BV) vs FOLFIRI-BV with biomarker stratification as first-line (1L) chemotherapy (CT) in patients (pts) with metastatic colorectal cancer (mCRC).

Abstract

493 Background: Standard 1L mCRC treatment (tx) includes a CT backbone (e.g., modified leucovorin [LV]/5-fluorouracil [5-FU]/oxaliplatin [mFOLFOX6] or LV/ 5-FU/ irinotecan [FOLFIRI]) and biologic therapy (e.g., BV). The preferred CT backbone for anti VEGF tx is unknown. MAVERICC (NCT01374425), a global, randomized, open-label, phase 2 trial, assessed tx efficacy and safety of mFOLFOX6-BV vs FOLFIRI-BV in pts with mCRC. Intratumoral ERCC1 and plasma VEGF-A were studied as biomarkers for oxaliplatin- and BV-containing tx, respectively. Methods: Pts with mCRC (≥1 measurable metastatic lesion, ECOG performance status ≤1) were randomized 1:1 to receive BV (5 mg/kg) + mFOLFOX6 or FOLFIRI every 2 weeks, stratified by ERCC1 level (low [£1.7] vs high [>1.7]) and region. VEGF-A levels were measured at baseline. Primary objectives were to evaluate: ERCC1 as a biomarker of progression-free survival (PFS) in 1L mCRC tx (mFOLFOX-BV vs FOLFIRI); and VEGF-A as a biomarker for BV and as a biomarker in combination with ERCC1 for PFS following CT + BV. Secondary objectives were to evaluate: the effect of ERCC1 and VEGF-A on overall survival (OS), objective response rate, hepatic metastases resection, and safety. PFS and OS were estimated by Kaplan–Meier methods, hazard ratios (HR) were estimated by Cox regression, and p-values were based on stratified log-rank tests. ERCC1 biomarker analyses are presented here. Results: A total of 376 pts were randomized: median age, 61 yr; white race, 83%; US region, 85%. Baseline characteristics: ERCC1 high, 35%; KRAS mutant, 34%. Efficacy results are shown (see Table). Conclusion: Consistent with previous findings, PFS and OS were comparable in pts treated with either 1L mFOLFOX6-BV or FOLFIRI-BV. Exploratory analyses within pts with high ERCC1 levels suggest consistent results. VEGF-A analyses are ongoing. Clinical trial information: NCT01374425. [Table: see text] [Table: see text]

Early Tumor Shrinkage and Depth of Response as Predictors of Favorable Treatment Outcomes in Patients with Metastatic Colorectal Cancer Treated with FOLFOX Plus Cetuximab (JACCRO CC-05)

“…The relative dose intensity of 68.8 % for oxaliplatin was lower than that in the OPUS trial, with no apparent negative effect on efficacy. The median number of administered cycles of oxaliplatin in our study was 10, similar to the 11 cycles in the modified-FOLFOX6 arm of the recently reported MAVERICC study [16].…”

Precision treatment in colorectal cancer: Now and the future

“…It has therefore been proposed as a surrogate biomarker for oxaliplatin resistance. However, clinical trials have not demonstrated the predictive ability of ERCC1 in oxaliplatin‐based treatment . Thus, EMSO has not recommended ERCC1 testing prior to the use of oxaliplatin in routine practice …”

Predictive and prognostic biomarkers in personalized gastrointestinal cancer treatment

“…KRAS status has also been evaluated as a prognostic biomarker. A recent analysis of the MAVERICC trial evaluated the prognostic role of KRAS (18). This phase 2 randomized clinical trial compared the combination of FOLFOX plus bevacizumab vs. FOLFIRI plus bevacizumab, with KRAS found to be a prognostic biomarker.…”