大腸がんの治療成績は同等である（Abstract: LBA3）

Results from a large phase III study demonstrate that four common first-line treatment regimens – bevacizumab plus chemotherapy and cetuximab plus chemotherapy – are equally effective for patients with metastatic colorectal cancer and no KRAS mutations. In the study, the median overall survival was roughly 29 months with either approach. The data also suggest that either FOLFOX (oxaliplatin/5-fluorouracil/leucovorin) or FOLFIRI (irinotecan/5-fluorouracil/leucovorin) chemotherapy regimens are acceptable in combination with either of the two targeted drugs.

"About 75 percent of patients with metastatic colorectal cancer in the United States initially receive bevacizumab-based therapy, although we know that cetuximab-based therapy is also a good option for a subset of patients," said lead author Alan P. Venook, M.D., the Madden Family Distinguished Professor of Medical Oncology and Translational Research at the University of California in San Francisco, CA. "Our findings clearly show that the two antibodies – with either FOLFOX or FOLFIRI – are both acceptable, and similarly effective. This should reassure doctors and patients facing decisions about treatment selection."

Each year, about 50,000 Americans are diagnosed with metastatic colorectal cancer. Targeted therapies have played a key part in extending survival for patients with metastatic colorectal cancer, from 10 months 20 years ago to the nearly 2.5 years seen in this study. Bevacizumab targets VEGF, blocking the development of blood vessels that tumors need to grow, while cetuximab targets EGFR, a protein involved in cancer growth and spread. Bevacizumab with FOLFOX is widely used in the United States, while cetuximab-based regimens tend to be used more frequently in Europe.

In the study, 1,137 patients with untreated metastatic colorectal cancer were randomly assigned to receive bevacizumab plus chemotherapy or cetuximab plus chemotherapy. The selection of chemotherapy was based on physician preference (26.6 percent received FOLFIRI, 73.4 percent FOLFOX). The median follow-up was 24 months.

There were no significant differences in either overall or progression-free survival between the treatment groups. In the bevacizumab plus chemotherapy group, the overall and progression-free survival were 29 months and 10.8 months, respectively, and 29.9 months and 10.4 months respectively in the cetuximab plus chemotherapy group.

No new treatment side effects were detected in this study. Common side effects of bevacizumab are high blood pressure, headache, mouth sores, nosebleed, diarrhea, bleeding from the rectum, loss of appetite, fatigue, and weakness, and the most common side effects of cetuximab are acne-like rash, itching, changes in fingernails and toenails, infections, fatigue, and low blood electrolyte levels. Costs of bevacizumab and cetuximab are comparable but side effects are slightly different. FOLFIRI and FOLFOX also differ in side effects ─ FOLIFIRI causes more hair loss and diarrhea but FOLFOX causes neuropathy that often necessitates stopping treatment. Updated analyses show that the overall quality of life for patients on either of the antibodies is similar.

Dr. Venook remarked that this kind of head-to-head comparative clinical trial comparing two agents from different companies with similar indications probably would not have been possible without the nation's investment in clinical trials led by the National Cancer Institute. "This study shows that we are still doing good, important work, even in the era of reduced funding for cooperative groups," he said.
Forthcoming analyses from this study will explore benefits of these approaches in different subsets of patients. Genomic profiling will be conducted to identify potential prognostic markers, which might be helpful in selecting optimal treatments for individual patients in the future.

ASCO Perspective: "With this finding, oncologists and patients have more ways to personalize cancer treatment," said ASCO president Clifford A. Hudis, M.D., FACP. "They can be reassured that two widely used regimens offer good and equivalent survival."

This research was supported in part by the National Cancer Institute, National Institutes of Health; Imclone; Roche; Genentech; BMS; and Eli Lilly.