First-line treatment regimens for patients with metastatic colorectal cancer without KRAS mutations – bevacizumab + chemotherapy and cetuximab + chemotherapy ? are equally effective. This conclusion is based on data from a large federally funded phase III study analyzing four common first-line treatment regimens. In the study, the median overall survival was roughly 29 months with either approach. The study was, in part supported the National Cancer Institute (NCI), Imclone, Genentech/Roche, Bristol-Myers Squibband Eli Lilly.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% 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,? noted lead author Alan P. Venook, MD, the Madden Family Distinguished Professor of Medical Oncology and Translational Research at the University of California and Professor of Clinical Medicine, Division of Hematology Oncology, Department of Medicine Chairman, UCSF Committee on Human Research 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, 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.
Study data
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% received FOLFIRI, 73.4% 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.
This study shows that we are still doing good, important work, even in the era of reduced funding for cooperative groups…
Adverse events
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.
Head-to-head comparison
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 noted. 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.
Personalized Treatment
?With this finding, oncologists and patients have more ways to personalize cancer treatment,? said 2013 – 2014 ASCO president Clifford A. Hudis, MD, FACP., Chief, Breast Cancer Medicine Service, at Memorial Sloan Kettering, New York, NY.?They can be reassured that two widely used regimens offer good and equivalent survival.?
For more information:
Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Mahoney MR, O’Neil BH, Shaw JE, Polite BN, et al. CALGB/SWOG 80405: Phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC). ASCO 2014 Annual Meeting, Plenary Session, Sunday June 1, 1:00 PM to 4:00 PM, Abstract No: LBA3 Citation: J Clin Oncol 32:5s, 2014 (suppl; abstr LBA3)[Abstract]
Photo: Alan P. Venook, MD at the American Society of Clinical Oncology Annual Meeting, Sunday June 1, 2014. Photo Courtesy: ?ASCO/Phil McCarten
