Randomized phase II study of cetuximab versus irinotecan and cetuximab in patients with chemo-refractory KRAS codon G13D metastatic colorectal cancer (G13D-study)

PURPOSE: This study investigated the efficacy and safety of cetuximab-based treatment in patients with chemotherapy-resistant refractory mCRC with KRAS G13D mutation. PATIENTS AND METHODS: An assessment of the efficacy and safety of cetuximab-based treatment was performed in an observation-enriched randomized controlled study comparing the cetuximab alone group (Cet group) and the combination of cetuximab and irinotecan group (CetI group) for KRAS G13D-mutated mCRC in Japan. In this study, the patients received a biweekly (500 mg/m(2) on day 1) or weekly (250 mg/m(2)) intravenous infusion of cetuximab in Cet group, or a biweekly (500 mg/m(2) on day 1) or weekly (250 mg/m(2)) intravenous infusion of cetuximab followed by irinotecan (150 mg/m(2)) in CetI group. Propensity score adjustment was used to achieve balance in the observational arm. RESULTS: Data from a total of 29 patients (10 in Cet group, 19 in CetI group) were analyzed. Crude median progression-free survival time was 2.9 months in the Cet group and 2.5 months in the CetI group. Crude disease control rates were 55.6% in the Cet group and 47.4% in the CetI group. After a median follow-up of 43 months, the crude median overall survival was 8.0 months in the Cet group and 7.6 months in the CetI group. Cetuximab-based treatment did not markedly increase any characteristic toxicity and was generally well tolerated. Propensity score analyses adjusted for performance status and number of metastases showed comparable results with the crude results. CONCLUSION: Cetuximab-based treatment seemed to benefit patients with chemotherapy-resistant, refractory KRAS G13D-mutated mCRC. Our results might support the administration of cetuximab-based treatment for KRAS-mutant mCRC and would be able to provide treatment flexibility in this setting.