Erbitux edges ahead of Avastin for newly diagnosed metastatic colorectal cancer

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In the FIRE-3 study, Erbitux (cetuximab) came out ahead in overall survival when compared with Avastin (bevacizumab) when treating patients with newly diagnosed metastatic colorectal cancer. However, the end result was that the overall response rate (ORR), which was the main focus of the study, was similar in both arms, which leads experts wondering what to make of the results.

Nearly 600 patients were given either drug with the chemotherapy regimen FOLFIRI. ORR in patients was comparable, as was progression-free survival at around 10 months. Overall survival was 28.7 months in the Erbitux arm compared with 25 months with Avastin. (Abstract #3506.) Expert discussion after the presentation hypothesized that because more patients dropped out of the Erbitux arm for some reason may have skewed the results just a touch. There's also the possibilities that progression-free survival and overall survival, which researchers have assumed correlated in the past, may not in certain targeted therapies. That would certainly change the outlook on trial designs for the future.

In any case, Richard M. Goldberg, physician-in-chief at The Ohio State University Comprehensive Cancer Center, said he would feel comfortable using either drug, and if you use Erbitux first, it leaves Avastin as a valid option for second-line therapy. He also encouraged the researchers to examine the later therapies the patients received to help make sense of the data. That analysis will be presented at a later meeting this year.

The two targeted therapies work differently as Erbitux inhibits a pathway that contributes to cancer cell growth, while Avastin halts blood vessel growth to the tumor. All patients were confirmed not to have a KRAS mutation in their tumor--KRAS mutation-positive cancers do not respond to EGFR-targeted agents such as Erbitux. Side effects were common in both groups, including neutropenia, diarrhea, nausea and fatigue. Patients in the Erbitux arm experienced more skin-related effects.

Experts noted the drugs are also being studied in combination with FOLFOX, a more common chemotherapy regimen in the U.S. Results of that trial will be available at the end of the year, and may provide physicians more answers into when to use these targeted drugs.

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