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First-line bevacizumab, cetuximab equally effective for metastatic colorectal cancer
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CHICAGO — Patients with KRAS wild-type, metastatic colorectal cancer demonstrated similarly prolonged OS whether they received first-line bevacizumab or cetuximab with chemotherapy, according to results of a phase 3 study presented at the ASCO Annual Meeting.
“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,” Alan P. Venook, MD, lead author and Madden Family Distinguished Professor of Medical Oncology and Translational Research at the University of California in San Francisco, said in a press release. “Our findings clearly show that the two antibodies — with either FOLFOX or FOLFIRI — are both acceptable, and similarly effective.”
Venook and colleagues evaluated data from 1,137 patients who received FOLFIRI (26.6%; irinotecan [Camptosar, Pfizer], 5-FU and leucovorin) or mFOLFOX6 (73.4%; oxaliplatin, 5-FU and leucovorin) chemotherapy according to physician preference. The median age of patients was 59 years, and 61% were male.
Researchers then assigned 578 patients to receive their chemotherapy with a 400-mg/m2 loading dose of cetuximab (Erbitux, Eli Lilly) followed by 250 mg/m2 weekly doses. The other 559 patients received chemotherapy plus 5 mg/kg biweekly bevacizumab (Avastin, Genentech).
Median follow-up was 24 months.
Patients who received bevacizumab achieved an OS of 29.04 months, which was comparable to the 29.93-month median OS achieved among patients who received cetuximab (HR=0.92; 95% CI, 0.78-1.09).
Although there were no statistical differences between the arms, the 29-month OS seen with both treatments is a new benchmark for care in this setting, Venook said.
Median PFS also was similar between the two arms (bevacizumab, 10.84 months; cetuximab, 10.45 months).
An updated analysis after a median follow-up of 40 months (range, 8-86 months) indicated 94 patients were disease-free following surgery. Further analyses on expanded RAS, FOLFOX vs. FOLFIRI and subsequent therapies are underway.
Researchers noted no unexpected toxicities occurred, and quality of life was similar between the arms.
“These two distinctly different biological therapies in combination with chemotherapy did not impart a different outcome for the patients receiving either one,” Venook said. “For patients, this tells us either FOLFIRI or FOLFOX with either bevacizumab or cetuixmab are perfectly reasonable options for first-line therapy for this population of patients. Essentially patients and doctors have four choices of therapy they might initiate, and patients can make this decision based on preference in terms of toxicity or other issues because these appear to have equivalent long-term outcomes.”
For more information:
Venook AP. Abstract #LBA3. Presented at: ASCO Annual Meeting; May 30-June 3, 2014; Chicago.
Disclosure: The study was funded by Bristol-Myers Squibb, Eli Lilly, Genentech, ImClone, the NCI and Roche. Researchers report consultant/advisory roles with, research funding or honoraria from Bayer, Bristol-Myers Squibb, Genentech, Lilly, Onyx, Roche and Sanofi.
Perspective
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Clifford A. Hudis, MD, FACP
While on the one hand there may be some temptation to tag this as a negative trial since the two arms are the same, the really important thing is that this sets an entirely new standard and new high bar for clinical trials in advanced colorectal cancer.
It also highlights the reason we need and will continue to need significant investment [in research]. With each incremental improvement, the size of the subsequent trial statistically is unfortunately going to have to get larger to see those differences. This incremental improvement is a great problem to have, but it highlights the critical role of the federally supported public funding to get this kind of work launched.
Perspective
Back to TopJosep Tabernero, MD, PhD
We still have several essential questions that will occur with further clinical and preclinical evaluation, including the specific interaction of the biological agents with chemotherapy, treatment sequence, and correlation with some important clinical marker characteristics related to the primary tumor location and molecular subtypes.
For the time being, cetuximab added to standard chemotherapy — primarily FOLFOX — is not superior to bevacizumab in the first-line treatment of patients with KRAS exon 2 wild-type metastatic colorectal cancer; however, expanded OS analysis may change this statement in the near future. That 80% were presented FOLFOX and cetuximab may make the National Comprehensive Cancer Network reconsider its position in the metastatic colorectal cancer guidelines. The treatment choice for each patient should consider efficacy, safety, cost, lack of availability and similarly important individual parameters. Importantly, the median survival for patients with metastatic colorectal cancer has reached a new benchmark of about 30 months.
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