Final analysis of the randomized trial of the German AIO CRC study group: Cetuximab plus XELIRI versus cetuximab plus XELOX as first-line treatment for patients with metastatic colorectal cancer (mCRC).

Abstract

3540 Background: Cetuximab combined with 5-fluorouracil/folinic acid plus irinotecan or oxaliplatin has shown activity in the treatment of mCRC. This randomized phase II trial investigated the efficacy and safety of the epidermal growth factor receptor antibody cetuximab combined with the oral fluoropyrimidine capecitabine plus irinotecan (XELIRI) or oxaliplatin (XELOX) in the first-line treatment of mCRC. Methods: A total of 185 mCRC patients were randomized to cetuximab (400 mg/m2 day 1, followed by 250 mg/m2 weekly) plus XELIRI (irinotecan 200 mg/m2, day 1; capecitabine 800mg/m2; twice daily days 1-14, every 3 weeks; 20% dose reduction of both agents for patients older than 65 years) or cetuximab plus XELOX (oxaliplatin 130 mg/m2 day 1; capecitabine 1,000 mg/m2 twice daily days 1- 14, every three weeks). The primary study endpoint was objective response rate (ORR). KRAS mutation status (wild type or mutant) was determined on codons 12/13 using a mutation-specific quantitative PCR-based assay. Results: In the intention-to-treat patient population (n = 177), ORR was 46.1% (95% CI: 35.4-57) versus 47.7% (95% CI: 37-58.7) and the disease control rate 74.2% versus 77.3% for cetuximab plus XELIRI versus cetuximab plus XELOX. Time to progression and overall survival were 6.3 and 21.1 months for cetuximab and XELIRI compared to 7.7 and 25.5 months for cetuximab and XELOX. Secondary resection was possible in 9.2% of patients with liver metastases. Both study treatments had manageable tolerability profiles and were safe. The most common grade 3/4 toxicities in the cetuximab plus XELIRI arm versus cetuximab plus XELOX arm were diarrhea (15.7% versus 19.3%), cetuximab-induced exanthema (12.4% versus 20.5%), and sensory neurotoxicity (1.1% versus 14.8%). KRAS analysis data will be presented at the meeting. Conclusions: This randomized trial demonstrates the efficacy and tolerability of cetuximab combined with XELIRI or XELOX for the first-line treatment of patients with mCRC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck, Roche Merck, Pfizer, Roche, sanofi-aventis Merck, Pfizer, Roche, sanofi-aventis