LOS ANGELES—In colorectal cancer patients progressing after second- and third-line therapies, cetuximab (Erbitux) is an option that may prolong progression-free and overall survival, according to phase III studies presented at the American Association for Cancer Research 2007 centennial annual meeting.

When administered in the third-line setting, cetuximab improved survival by 23%, compared with best supportive care (BSC), in the NCIC CO.17 trial (abstract LB-1), reported Derek Jonker, MD, assistant professor, University of Ottawa, and the Canadian co-chair of the study. The trial was conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), in collaboration with the Australasian Gastro-Intestinal Trials Group (AGITG). "This is the first time a single biologic targeted agent has demonstrated a survival advantage in patients with colorectal cancer, and the first time an EGFR-targeting drug has achieved this goal," Dr. Jonker said.

NCIC CO.17 enrolled 572 colorectal cancer patients with EGFR detectable by immunohistochemistry. Patients had received an anti-thymidylate synthase inhibitor—5-fluorouracil or capecitabine (Xeloda)—and had failed both irinotecan (Camptosar) and oxaliplatin (Eloxatin) (unless these drugs were contraindicated). Patients were randomized to BSC alone (n = 285) or BSC plus cetuximab 400 mg/m2 loading dose followed by a weekly infusion of 250 mg/m2 (n = 287). The primary endpoint was overall survival. The final analysis was performed when 456 deaths were observed.

Survival Improved

Patients receiving cetuximab had a 23% reduction in mortality and a 32% reduction in the risk of disease progression. Median survival was 6.1 months in the cetuximab arm and 4.6 months in the BSC arm, producing a hazard ratio (HR) of 0.77 (P = .0046). All subgroups (age, performance status, sex) experienced a survival benefit. Median progression-free survival was 1.9 vs 1.8 months (HR 0.68. P < .0001). The benefits in terms of overall survival and time to progression were robust even after adjustments were made for multiple baseline variables, Dr. Jonker added.

Objective responses were observed in 19 patients (6.6%) receiving cetuximab but in no patients (0%) assigned to BSC (P < .0001). Stable disease was observed in 84 patients (29.3%) and 29 patients (10.2%), respectively, for a disease control rate of 35.9% vs 10.2%.

Skin Toxicity

In an exploratory analysis, skin toxicity was strongly correlated with response and survival. Median survival was 2.6 months in patients with no rash, 4.8 months in those with grade 1 rash, and 8.4 months in those with grade 2+ rash.

The safety profile was consistent with other cetuximab studies. Grade 3+ toxicities were significantly more frequent in the cetuximab arm, including rash/desquamation (12% vs 0%), infection without neutropenia (13% vs 5%), confusion (6% vs 0%), other pain (15% vs 7%), and hypomagnesemia (6% vs 0%). Grade 3 anemia, however, was more common with BSC alone (4% vs 11%).