Merck KGaA announced that the German cooperative investigator group AIO (Arbeitsgemeinschaft Internistische Onkologie) reported new data from the Phase 3 head-to-head clinical trial FIRE-3, which show a clinically relevant improvement from Erbitux (cetuximab) plus FOLFIRI versus bevacizumab plus FOLFIRI as first-line treatment in metastatic colorectal cancer (mCRC) in patients with RAS wild-type tumors.
The new data, from a preplanned exploratory analysis, were presented at the European Cancer Congress 2013 (ECCO-ESMO-ESTRO). The analysis shows a 7.5 month increase in median overall survival (OS) in mCRC patients with RAS wildtype tumors, receiving first-line Erbitux plus FOLFIRI compared with patients receiving bevacizumab plus FOLFIRI (OS: 33.1 months vs. 25.6 months, respectively). In a post hoc analysis of the patient group with any RAS mutations, patients who received Erbitux plus FOLFIRI first-line reached an OS of 20.3 months vs. 20.6 months in the group that was treated with bevacizumab plus FOLFIRI.
As previously presented at the annual meeting of the American Society of Clinical Oncology (ASCO) 2013 and at the World Congress on Gastrointestinal Cancer 2013, the primary endpoint of the trial, objective response rate based on investigators’ read in patients with KRAS exon 2 wild-type tumors, was not met. In the patient group with KRAS exon 2 wild-type tumors, an expected and balanced cross-over or continuation beyond progression with regard to subsequent biologic treatments in second line therapy (either EGFR antibody or bevacizumab) was observed. Also, no major imbalances were noted with regard to chemotherapies used in second line treatment. It is important to note that this result is not fully mature (57 percent event rate in the “intent-to-treat” KRAS exon 2 wild-type population) and will be updated in due course.
“These new data from the Phase 3 study FIRE-3 show a 7.5-month increase in median overall survival to 33.1 months when using first-line Erbitux plus FOLFIRI as compared to using bevacizumab plus FOLFIRI in metastatic colorectal cancer. Such a prolongation is a paradigm shift in mCRC treatment since the introduction of monoclonal antibodies,” said Professor Volker Heinemann from the Ludwig Maximilians University, Munich, and FIRE-3 principal investigator. “Together with insights from other recent relevant studies, these results suggest that first-line treatment of RAS wild-type patients should include an anti-EGFR therapy.”
“These results continue to reinforce the value of Erbitux as a first-line treatment for metastatic colorectal cancer and show that RAS tumor status is likely to help to identify those patients who are most likely to benefit from Erbitux,” said Dr. Annalisa Jenkins, head of Global Drug Development and Medical at the Merck Serono division. “Additional biomarker analyses are being conducted on data from the pivotal Erbitux studies, CRYSTAL and OPUS to help shed additional light on the role of RAS mutations in these patients.”
Date: September 28, 2013
Source: Merck KGaA
