Cetuximab versus Bevacizumab: Comparable Benefit as First-Line Therapy for Metastatic Colorectal Cancer

June 2014, Vol 5, No 5

Chicago, IL—A head-to-head comparison of 2 monoclonal antibodies for metastatic colorectal cancer (mCRC) has shown no difference in their benefit when paired with chemotherapy in the first-line setting.

The results of the phase 3, federally funded CALGB/SWOG 80405 trial were presented at a 2014 American Society of Clinical Oncology (ASCO) meeting plenary session by Alan P. Venook, MD, Madden Family Distinguished Professor of Medical Oncology and Translational Research, University of California, San Francisco.

The optimal monoclonal antibody to pair with chemotherapy in the first-line treatment of mCRC has been unclear. US oncologists tend to use bevacizu­mab (Avastin) more than ce­tuximab (Erbitux), but the recent European FIRE-3 study showed that cetuximab had an overall survival (OS) benefit, although, puzzlingly, no benefit in progression-free survival (PFS).

“In CALGB/SWOG 80405, we did not show a meaningful difference between cetuximab and bevacizumab. These 2 distinctly different biologic treatments did not impart differences in outcomes. Either is appropriate in the first-line metastatic setting,” said Dr Venook.

In 2004, when the study was designed, bevacizumab and cetuximab had just been approved, and although they had different toxicity profiles, their relative efficacy was unknown. CALGB/SWOG 80405 underwent 14 amendments and 11 interim analyses, reflecting the rapidly evolving treatment landscape of colorectal cancer in the past 15 years, Dr Venook noted.

“The question was, which was the optimal first-line treatment?” he asked. “The assumption at the start was that maybe one was better.”

High Survival Rates in Both Arms
The CALGB/SWOG 80405 randomized 1137 previously untreated patients with KRAS wild-type (codons 12, 13) to chemotherapy (by physician’s choice) plus bevacizumab or cetuximab. Of these patients, 75% of patients received FOLFOX (5-fluorouracil [5-FU]/leucovorin/oxaliplatin [Eloxatin]), and 25% received FOLFIRI (5-FU/leucovorin/irinotecan [Camptosar]).

At a median follow-up of 24 months, no significant differences were seen between the 2 groups in OS, which was 29 months with bevacizumab (plus chemotherapy) and 29.9 months with cetuximab (plus chemotherapy). The PFS was 10.8 months and 10.4 months, respectively.

With the exception of 1 small study, the median OS of >29 months is the longest yet recorded in a trial of patients with mCRC. In the late 1980s, the median survival was just 8 months, according to Dr Venook, who called this OS benefit “unprecedented.”

No new toxicities emerged in this study, Dr Venook noted.

“Our findings clearly show that the 2 antibodies—with either FOLFOX or FOLFIRI—are both acceptable and similarly effective. First-line therapy should reflect the patient’s preference or concern for potential side effects.”

The findings of the current study are different from those of the European FIRE-3 trial reported last year, in which cetuximab improved OS.

The Value of Federally Funded Trials
“These patients are doing a little better, and I believe this represents a less biased approach. This is what cooperative groups do: treat patients in studies for which companies are not paying the bill,” Dr Venook said in a press briefing.

He did not predict that the comparability between the arms would lead to more prescriptions for cetuximab, however, “since patients don’t like skin rash.” Expanded RAS testing and other molecular and clinical analyses may identify subsets of patients who get more or less benefit from the specific regimens.

ASCO President Clifford A. Hudis, MD, Chief, Breast Cancer Medicine Service, Memorial Sloan Kettering Cancer Center, New York, who moderated the press briefing, commented, “The really impor­tant thing is that this sets a new standard and a new high bar for clinical trials in advanced colorectal cancer. It also highlights the reason that we will continue to need significant investment. With each incremental benefit, the size of trials will need to get larger to see differences.”

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