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Analyses of two large, randomized, phase III trials found cetuximab helped to preserve quality of life for patients with advanced colorectal cancer.
The National Cancer Institute of Canada (NCIC) and the Australasian Gastro-Intestinal Trials Group compared cetuximab (Erbitux) plus best supportive care with best supportive care alone in an evenly randomized study of 572 patients with metastatic colorectal cancer.
"The trial accomplished its primary health-related quality of life end point by demonstrating improved physical function and global health status change scores at 8 and 16 weeks with cetuximab compared to best supportive care alone," reported Dr. Heather-Jane Au of the NCIC.
The Erbitux Plus Irinotecan in Colorectal Cancer (EPIC) trial accrued 1,298 metastatic colorectal patients at 221 centers in the United States and Europe. New data showed that health-related quality of life was better maintained with cetuximab and irinotecan than with single-agent irinotecan (Camptosar). Patients in the combination arm had less deterioration in global health scores and in symptom scores for pain, nausea, and insomnia.
Dr. Cathy Eng, of the University of Texas M.D. Anderson Cancer Center in Houston, reported changes from baseline favored the combination with respect to physical functioning, role functioning, emotional functioning, and cognitive functioning. Patients also had more significant improvements in fatigue, nausea, pain, diarrhea, and insomnia. "The combination of irinotecan plus cetuximab resulted in better quality of life despite increased diarrhea and fatigue compared to irinotecan alone," she said.
The NCIC trial found cetuximab significantly prolonged overall survival and progression-free survival with improved response compared with best supportive care alone. Patients in the best supportive care alone arm had worsening of global health status and physical function at 8 and 16 weeks,
In EPIC, cetuximab failed to improve overall survival. Dr. Eng said this might be because about half the patients in the irinotecan-only arm received cetuximab after the trial. EPIC did show significant gains in progression-free survival and response with cetuximab.
Men comprised about two-thirds of both trial populations, with median ages in the early 60s. Both trials used the self-reported European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 for quality of life analyses, and both reported that questionnaire compliance decreased over time. In EPIC, it began to fall after the first cycle of chemotherapy, diminishing to about 50% at 33 weeks.
"It's plausible that the best supportive care patients were unable to complete their questionnaires because they were doing more poorly, so it may be that the health-related quality of life differences that we've demonstrated in NCIC are conservative," Dr. Au said.
With more multiple-treatment regimens available and survival times increasing, it's important that quality of life be integrated into clinical trial outcome measures, discussant Dr. Edith P. Mitchell observed. "From these two studies, we can say there are correlations between quality of life and other outcome measures ... first in the NCIC study with improvements in overall survival, progression-free survival, and response rates, and in the EPIC trial with progression-free survival and response," said Dr. Mitchell, of Thomas Jefferson University in Philadelphia.
Dr. Au reported receiving a research grant from Bristol-Myers Squibb; it and Merck KGaA previously reported providing partial funding for EPIC.
Au H. et al. Quality of life in patients with advanced colorectal cancer treated with cetuximab: Results of the NCIC CTG and AGITG CO.17 trial. Abstract 4002.
Eng C. et al. Impact on quality of life of adding cetuximab to irinotecan in patients who have failed prior oxaliplatin-based therapy: The EPIC trial. Abstract 400.
Commentary |
EPIC, a multinational phase III trial, found health-related quality of life was better preserved in colorectal cancer patients receiving cetuximab plus irinotecan, compared with irinotecan alone. A second study, of 572 patients, concluded that cetuximab provides palliation in pretreated patients with advanced colorectal cancer. I believe it means that the addition of a biologic such as cetuximab can benefit patients by providing palliation, presumably due to stabilization of disease and/or response. — Stuart M. Lichtman, M.D.
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