Cetuximab weekly (q1w) versus every two weeks (q2w) plus FOLFOX4 as first-line therapy in patients (pts) with KRAS wild-type (wt) metastatic colorectal cancer (mCRC).

Abstract

494 Background: FOLFOX4 + q1w cetuximab is a standard 1st-line regimen in KRAS wt mCRC. This trial evaluated FOLFOX4 + q1w cetuximab (Arm A) and FOLFOX4 + q2w cetuximab (Arm B) as 1st-line therapy in KRAS wt mCRC. Methods: Pts with KRAS wt mCRC were randomized to q1w cetuximab (400 mg/m2initial dose then 250 mg/m2/wk) or q2w cetuximab (500 mg/m2 every 2 wks). Both arms received FOLFOX4 (folinic acid 200 mg/m2, then 5-FU 400 mg/m2bolus, then 5-FU 600mg/m2 over 22 h on days 1+2, plus oxaliplatin 85 mg/m2 on day 1 q2w). Primary endpoint is objective response rate (ORR) which was analyzed in a protocol specified interim analysis. Secondary efficacy endpoints are progression- free survival (PFS) and overall survival. Results: From Sep 2007 to Sep 2009, 152 pts with KRAS wt tumors (22 centers in 12 countries) were randomized and received ≥1 dose of study treatment, arm A (n=75) and arm B (n=77). Baseline characteristics were well balanced (A vs B): mean age: 57 vs 60 years, Karnofsky Performance Score (PS) 80: 15% vs 18%, PS 90: 45% vs 40%, PS 100: 40% vs 42%, male gender: 40% vs 45%, prior adjuvant or neoadjuvant therapy: 23% vs 17%, metastases at initial diagnosis: 65% vs 64%, and >2 involved organs: 24% vs 29%. Median follow up was 12 months. ORR (CR + PR) was 51% in arm A and 63% in arm B, respectively, the difference between arm B and A was 12% (95% CI: -4% to 27%). Preliminary results for PFS time did not indicate relevant differences between both arms. Mature PFS results will be presented at the symposium. Based on current data, most common grade 3-4 adverse events (≥ 10% in any arm, A vs B) were neutropenia/neutrophil count decreased in 32 vs 34%, rash in 15 vs 16% and diarrhea in 7 vs 10% of the pts. Conclusions: These data suggest that cetuximab q2w has comparable efficacy and an equivalent safety profile as q1w dosing in combination with FOLFOX4. Data collection and analysis is ongoing. [Table: see text] [Table: see text]