In patients with chemotherapy-refractory metastatic colorectal cancer (mCRC) harboring the exon 2 KRAS G13D mutation, there was no statistically significant improvement in disease control at 6 months with either single-agent cetuximab or cetuximab plus irinotecan, according to findings published in the Journal of Clinical Oncology.1

Although RAS mutations predict lack of response to epidermal growth factor receptor (EGFR) monoclonal antibody therapies like cetuximab, preclinical studies and retrospective clinical findings suggest that patients with the exon 2 KRAS G13D mutation may derive benefit from cetuximab therapy.

Therefore, researchers sought to evaluate cetuximab monotherapy and in combination with irinotecan in chemotherapy-refractory patients with mCRC who have this rare molecular subtype.

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For the phase 2 ICECREAM trial, researchers enrolled 51 patients with KRAS G13D mutation-positive mCRC who had progressed within 6 months of irinotecan therapy. Participants were randomly assigned to receive cetuximab 400 mg/m2 as a loading dose, followed by 250 mg/m2 once weekly with or without irinotecan 180 mg/mg2 once every 2 weeks.

Results showed that the 6-month progression-free survival rate was 10% (95% CI, 2 – 26) with cetuximab monotherapy compared with 23% (95% CI, 9 – 40) for the combination (HR, 0.74; 95% CI, 0.42 – 1.32).

Researchers found that 0% of patients in the monotherapy arm and 9% of patients in the combination arm achieved a response. Stable disease was observed in 58% and 70%, respectively. The responses observed with the combination may represent true drug synergy or continued sensitivity to irinotecan. In addition, overall survival was similar between the 2 groups.

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In terms of safety, toxicities were more frequently reported in the patients that received irinotecan. Quality of life was similar between the 2 treatment arms.


  1. Segelov E, Thavaneswaran S, Waring PM, et al. Response to cetuximab with or without irinotecan in patients with refractory metastatic colorectal cancer harboring the KRAS G13D mutation: Australasian Gastro-Intestinal Trials Group ICECREAM study [published online ahead of print April 25, 2016]. J Clin Oncol. doi: 10.1200/JCO.2015.65.6843.