PURPOSE: The AIO KRK-0104 randomized phase II trial investigated the efficacy 
and safety of cetuximab combined with capecitabine and irinotecan (CAPIRI) or 
capecitabine and oxaliplatin (CAPOX) in the first-line treatment of metastatic 
colorectal cancer (mCRC).
PATIENTS AND METHODS: A total of 185 patients with mCRC were randomly assigned 
to cetuximab (400 mg/m(2) day 1, followed by 250 mg/m(2) weekly) plus CAPIRI 
(irinotecan 200 mg/m(2), day 1; capecitabine 800 mg/m(2) twice daily days 1 
through 14, every 3 weeks; or cetuximab plus CAPOX (oxaliplatin 130 mg/m(2) day 
1; capecitabine 1,000 mg/m(2) twice daily day 1 through 14, every 3 weeks). The 
primary study end point was objective response rate (ORR).
RESULTS: In the intention-to-treat patient population (n = 177), ORR was 46% 
(95% CI, 35 to 57) for CAPIRI plus cetuximab versus 48% (95% CI, 37 to 59) for 
CAPOX plus cetuximab. Analysis of the KRAS gene mutation status was performed in 
81.4% of the intention to treat population. Patients with KRAS wild-type in the 
CAPIRI plus cetuximab arm showed an ORR of 50.0%, a PFS of 6.2 months and an OS 
of 21.1 months. In the CAPOX plus cetuximab arm, an ORR of 44.9%, a PFS of 7.1 
months and an OS of 23.5 months were observed. While ORR and PFS were comparable 
in KRAS wild-type and mutant subgroups, a trend toward longer survival was 
associated with KRAS wild-type. Both regimens had manageable toxicity profiles 
and were safe.
CONCLUSION: This randomized trial demonstrates that the addition of cetuximab to 
CAPIRI or CAPOX is effective and safe in first-line treatment of mCRC. In the 
analyzed regimens, ORR and PFS did not differ according to KRAS gene mutation 
status.