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Cetuximab for KRAS Wild-Type Colorectal Cancer

First-line treatment with cetuximab was associated with benefits for progression-free survival and antitumor response, but not overall survival.

The monoclonal antibody cetuximab (Erbitux), which blocks the epidermal growth factor receptor (EGFR), has activity against colorectal cancer (CRC). However, benefits seem to be limited to patients who have KRAS wild-type tumors (JW Oncol Hematol Mar 3 2009).

Investigators conducted an industry-supported, multicenter phase III trial of cetuximab as part of first-line treatment for 1998 patients with metastatic, EGFR-positive CRC. Patients were randomized to receive fluorouracil, leucovorin, and irinotecan (FOLFIRI) alone or with cetuximab. Tumor KRAS status was evaluated retrospectively in 540 patients.

At median follow-up of 29.9 months for the cetuximab-FOLFIRI group and 29.4 months for the FOLFIRI-only group, patients who received cetuximab-FOLFIRI achieved longer median survival than those who received FOLFIRI alone (8.9 months vs. 8.0 months; hazard ratio, 0.85; P=0.048) and demonstrated higher antitumor response rate (46.9% vs. 38.7%; odds ratio, 1.4; P=0.004). Among patients with wild-type KRAS tumors (64.4% of patients tested), those who received cetuximab-FOLFIRI achieved longer median progression-free survival (PFS) than those who received FOLFIRI alone (9.9 months vs. 8.7 months; HR, 0.68; P=0.02) and demonstrated higher antitumor response rate (59.3% vs. 43.2%; OR, 1.91; P=0.004). Patients with mutant KRAS tumors who received cetuximab-FOLFIRI achieved PFS and antitumor response rates similar to those who received FOLFIRI alone. Overall survival was not influenced by the addition of cetuximab or by KRAS status.

Comment: As in other studies, benefits associated with cetuximab were limited to CRC patients with KRAS wild-type tumors. Thus, cetuximab should be reserved only for these patients. Investigators for the ongoing Cancer and Leukemia Group B Southwest Oncology Group 80405 trial will examine this issue further by comparing combination chemotherapy with either first-line cetuximab or bevacizumab (Avastin) in patients with advanced CRC.

— David H. Ilson, MD, PhD

Published in Journal Watch Oncology and Hematology May 19, 2009

Citation(s):

Van Cutsem E et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009 Apr 2; 360:1408.

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