O-0024 Phase 2 Randomized, Noncomparative, Open-Label Study of Aflibercept and Modified Folfox6 in the First-Line Treatment of Metastatic Colorectal Cancer (AFFIRM)

Abstract

ABSTRACT Introduction Aflibercept is a recombinant human fusion protein that acts as a decoy receptor preventing VEGF-A, VEGF-B, and PlGF from interacting with their receptors. The phase 3 VELOUR study demonstrated a statistically significant survival benefit with the combination of aflibercept + FOLFIRI in metastatic colorectal cancer (mCRC) patients who had progressed during or after prior oxaliplatin-based chemotherapy. Modified (m) FOLFOX6 is an established first-line regimen for patients with mCRC. Preclinical and clinical evidence supported the evaluation of aflibercept + mFOLFOX6 for the first-line treatment of patients with mCRC. An mFOLFOX6 study arm was included as a calibrator; the study was not powered for a statistical comparison. Methods The primary endpoint was progression-free survival rate at 12 months (PFS12). A secondary objective was to explore biomarkers. Patients with previously untreated mCRC, ECOG PS 0-2, and adequate organ function were randomized 1:1 to receive aflibercept 4 mg/kg + mFOLFOX6 (A) or mFOLFOX6 (B), every 2 weeks, and were stratified by ECOG PS (0-1/2), prior adjuvant therapy (yes/no), and metastases confined to liver (yes/no). Patients were to be treated to disease progression. PFS12 rate and objective response rate were assessed according to RECIST criteria by an Independent Review Committee blinded to treatment allocation. Results From March 2009 to April 2010, 236 patients (median age, 62.5 years; male, 61% PS 0-1, 97.5% prior adjuvant therapy, 10.2% liver metastases only, 28.4%) were randomized to A (n = 119) or B (n = 117). Baseline characteristics were similar in both arms. PFS12 was 25.8% (95% CI: 17.2-34.4) for A and 21.2% (95% CI: 12.2-30.3) for B. Response rate was 49.1% (95% CI: 39.7-58.6) in arm A and 45.9% (95% CI: 36.4-55.7) in arm B, and median PFS was 8.48 months (95% CI: 7.89-9.92) in arm A and 8.77 months (95% CI: 7.62-9.27) in arm B. Overall survival data had limited maturity, with less than 43% death events in each arm. Grade 3-4 adverse events with >5% higher incidence in arm A relative to arm B were hypertension, proteinuria, neutropenia, diarrhea, and infections. Biomarker data will be presented at the meeting. Conclusion In this phase 2 study, PFS12 with aflibercept + mFOLFOX6 appeared to be similar to mFOLFOX6, although the study was not powered for comparison. The biomarker analyses and clinical interpretation will be presented at the meeting. The safety profile of aflibercept was consistent with that seen in prior studies.