First-Line Cetuximab with Folfox or Folfiri Every 2 Weeks in Kras Wild-Type Metastatic Colorectal Cancer: Phase II Apec Study

Abstract

Background: Randomized studies have shown that the addition of weekly cetuximab to FOLFOX or FOLFIRI improves clinical outcome in the first-line treatment of patients with KRAS wild-type metastatic colorectal cancer (mCRC). This Asia-Pacific multicenter non-randomized phase II study investigated the efficacy and safety of both FOLFOX and FOLFIRI in combination with every 2 weeks cetuximab as first-line therapy in patients with KRAS wild-type mCRC. Methods: Eligible patients received every 2 weeks cetuximab (day 1, 500 mg/m2 every 14 days) with, based on investigator's choice, either FOLFOX (oxaliplatin 100 mg/m2, folinic acid [FA] 200 mg/m2 L-form or 400 mg/m2 racemic, then 5-fluorouracil [5-FU], as a 400 mg/m2 iv bolus and a 2400 mg/m2 infusion over 46 h) or FOLFIRI (irinotecan 180 mg/ m2, FA 200 mg/m2 L-form, or 400 mg/m2 racemic, then 5-FU, as a 400 mg/m2 iv bolus and a 2400 mg/m2 infusion over 46 h). Study treatment was continued until disease progression, the occurrence of unacceptable toxicity or consent withdrawal. The primary endpoint was tumor response; assessed radiologically (RECIST 1.0) every 8 weeks. Results: Data cut-off was 86 weeks after the date of the last patient included. The intention to treat (ITT)/safety population comprised 289 patients; 65.1% received FOLFOX plus cetuximab and 34.9% FOLFIRI plus cetuximab. Baseline characteristics were generally well balanced between treatment groups. However, leukocyte count >10000/mm3 was more frequent (16.5% vs 7.9%) and prior adjuvant treatment less frequent (21.3% vs 46.5%) in patients receiving FOLFOX plus cetuximab. A best overall response (complete + partial) rate of 58.8% and a median progression-free survival (mPFS) time of 11.1 months were observed in the combined ITT population (Table). 70.9% of patients showed ≥20% reduction in tumor diameter at 8 weeks from baseline. A post-hoc analysis showed a mPFS time of 12.7 months for this group. The overall R0 resection rate in the ITT population was 10.0%. Survival data are not yet mature. Cetuximab dose intensity was >80% in 77.7% of patients in the FOLFOX plus cetuximab group and 74.3% of patients in the FOLFIRI plus cetuximab group. The most frequent grade 3/4 adverse events (reported for >10% of patients in either arm) were neutropenia, diarrhea, hypokalemia, neuropathy (FOLFOX plus cetuximab group only) and skin reactions. Conclusion: In this study population from the Asia-Pacific region, first-line treatment with chemotherapy plus cetuximab was active and well-tolerated. Efficacy and safety profiles of every 2 weeks cetuximab combined with FOLFOX or FOLFIRI were similar to those reported for either chemotherapy plus weekly cetuximab in pivotal studies. (Table Presented).