Biweekly cetuximab plus irinotecan as second-line chemotherapy for patients with irinotecan-refractory and KRAS wild-type metastatic colorectal cancer according to epidermal growth factor receptor expression status

Abstract

Background Cetuximab plus irinotecan has been shown to be effective in metastatic colorectal cancer (mCRC) patients with wild-type (WT) KRAS and positive EGFR expressions (EGFR+). Retrospective analysis revealed that the efficacy of cetuximab was similar in mCRC patients negative (EGFR-) and positive for EGFR. However, the efficacy of cetuximab has not been assessed prospectively in EGFR- mCRC patients. Methods This was a prospective, multicenter phase II study assessed the efficacy and safety of biweekly cetuximab (500 mg/m²) and irinotecan (150–180 mg/m²) in patients with histologically proven adenocarcinoma with WT-KRAS and measurable lesion(s), either EGFR + or EGFR-, determined immunohistochemically, who failed first-line irinotecan-containing chemotherapy. The primary endpoint was response rate (RR), and the secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). Results Forty patients were enrolled; 20 EGFR + and 20 EGFR-; their baseline characteristics were balanced. The overall RR was 45% (18/40, 95% CI 29.6–60.4), 55% (11/20) in EGFR + and 35% (7/20) in EGFR- patients. Median PFS was 7.1 months (95% CI 4.8–9.4), 8.3 months in EGFR + and 4.9 months in EGFR- patients. Median OS was 18.5 months (95% CI 15.2–21.8), 17.2 months in EGFR + and 18.5 months in EGFR- patients. Grade 3 or 4 toxicities included neutropenia in 5 patients (12.5%) and febrile neutropenia/skin rash/asthenia in 2 (5%). Conclusions Biweekly cetuximab plus irinotecan as second-line treatment showed significant anti-tumor activity in patients with irinotecan-refractory mCRC and WT-KRAS regardless of EGFR expression status.