RESUMEN
BACKGROUND: The purpose of this study was to evaluate the combination of panitumumab and irinotecan in patients with KRAS wild-type metastatic colorectal cancer refractory to standard chemotherapy (oxaliplatin, fluoropyrimidines-irinotecan and bevacizumab). PATIENTS AND METHODS: KRAS status was first determined locally but subsequent validation of KRAS status and additional screenings (rare KRAS, NRAS, BRAF mutations and EGFR copy number) were centrally assessed. Patients received panitumumab (6 mg/kg) and irinotecan (180 mg/m²) every 2 weeks. RESULTS: Sixty-five eligible patients were analyzed. The objective response rate (ORR) was 29.2% [95% confidence interval (95% CI) 18.2-40.3]. Median progression-free and overall survivals were 5.5 and 9.7 months, respectively. Most frequent grade 3/4 toxic effects were skin 32.3%, diarrhea 15.4% and neutropenia 12.3%. Tissue samples were available for 60 patients. For the confirmed KRAS wild-type population codon 12 or 13 mutation (n = 54), ORR was 35.2% (95% CI 22.4.1-47.9). Thirteen patients had a NRAS, a BRAF or a rare KRAS mutation, and no tumor response was observed in this subgroup when compared with 46.3% (95% CI 31.1-61.6) ORR in the subgroup of 41 patients with no identified mutation. CONCLUSION: Panitumumab and irinotecan is an active third-line regimen in a well-defined population based on biomarkers. ClinicalTrials.gov Identifier NCT00655499.