Third-line single-agent cetuximab ups overall survival

Cetuximab (Erbitux) plus best supportive care (BSC) provided significantly better overall survival and progression-free survival, compared with BSC alone, in patients with advanced colorectal cancer who had failed or could not take all approved chemotherapies, according to an international research team.

Patients in the treatment group had a hazard ratio for death of 0.77 (P = .005) for overall survival and a hazard ratio for disease progression or death of 0.68 for progression-free survival (P < .001).

"This is the first time an antibody used as a single agent in colorectal cancer has demonstrated an overall survival benefit," noted Eric K. Rowinsky, MD, chief medical officer and senior vice president of ImClone, maker of Erbitux.

The company used the overall survival data to support cetuximab's use as a single agent in the third-line treatment of EGFR-expressing colorectal cancer patients after failure of both irinotecan (Camptosar)- and oxaliplatin (Eloxatin)-based regimens. FDA approved new labeling that included the survival results on October 2.

Details of the multicenter, open-label, randomized phase III trial, conducted by the National Cancer Institute of Canada Clinical Trials Group and the Australasian Gastro-Intestinal Trials Group, appeared in the New England Journal of Medicine (Jonker et al: 357:2040-2048, 2007).

The trial included 572 patients with EGFR-positive disease who had not responded to a fluoropyrimidine, irinotecan, and oxaliplatin (defined as unacceptable adverse events or progression within 6 months after completing treatment) or had contraindications to the drugs. All patients received BSC, defined as measures intended to palliate symptoms and improve quality of life.

Researchers administered cetuximab intravenously at an initial dose of 400 mg/m² of body surface area over 120 minutes, followed by weekly infusions of 250 mg/m² over 60 minutes. Treatments continued until death unless unacceptable adverse events, tumor progression, or worsening cancer symptoms occurred, or the patient requested that treatment end. Cetuximab treatment ranged from 1 to 60 weeks, with a median duration of 8.1 weeks. By the date of analysis, 222 of the 278 treatment patients and 234 of the 285 BSC-only patients had died. All but six deaths resulted from colorectal cancer.

Cetuximab-treated patients had a median overall survival of 6.1 months vs 4.6 months for the BSC-only group. Overall survival at 6 and 12 months was 50% and 21%, respectively, in the cetuximab-treated patients, and 33% and 16% in the group receiving only BSC. The estimated proportion of patients alive and progression-free at 3 and 6 months was 41% and 15%, respectively, in the treatment group, and 24% and 3% in the BSC-only arm.

Quality of life was better preserved in the cetuximab patients, with less deterioration in physical function and global health status scores (P < .05 for both).

Cetuximab was associated with a characteristic rash, and a rash of grade 2 or higher was strongly associated with improved survival (P < .001). Overall, grade 3–4 adverse events occurred more often in patients receiving cetuximab (78.5% vs 59.1% for BSC only). Specific grade 3-4 adverse events reported significantly more often with cetuximab were pain, infection without neutropenia, rash, and confusion.