Merck announced new biomarker findings from a retrospective analysis of the completed phase III study that compared Erbitux (cetuximab) plus FOLFIRI with FOLFIRI alone.
The analysis involved a subgroup of patients with KRAS wild-type (exon 2) metastatic colorectal cancer. A significant clinical improvement was observed in patients with RAS wild-type tumors when Erbitux was added to FOLFIRI in first-line mCRC. The data will be presented at the American Society of Clinical Oncology annual meeting June 2.
In the study, named CRYSTAL, 430 patient tumor samples with wild-type KRAS (exon 2) status were assessed for additional RAS mutations (defined as mutations in exons 3 or 4 of KRAS and/or exons 2, 3 or 4 of NRAS). Of these, 367 were RAS wild-type, while 63 presented a mutation.
The analysis showed a 27.7 percent increase in response rate, from 66.3 percent to 38.6 percent (95% CI: 2.03-4.78; p<0.0001). Median progression free survival increased by 3.0 months, 11.4 months compared to 8.4 months (HR: 0.56; 95% CI: 0.41-0.76; p=0.0002).
An 8.2-month increase in median overall survival was observed in mCRC patients with RAS wild-type tumors (n=367), at 28.4 months vs. 20.2 months, respectively (HR: 0.69; 95% CI: 0.54-0.88; p=0.0024).
In the patient group with either KRAS exon 2 mutations identified in the initial KRAS analysis (n=397) or other RAS mutations (n=63) receiving Erbitux plus FOLFIRI (n=246) no benefit was observed, compared with FOLFIRI alone (n=214). This subgroup analysis helps confirm the findings of other studies which have shown that patients with RAS mutations do not benefit from anti-EGFR therapy.
Following an update to the Erbitux label that was approved by the European Commission in December 2013, Erbitux is now indicated for the treatment of patients with epidermal growth factor receptor-expressing RAS wild-type mCRC in combination with irinotecan-based chemotherapy, in firstline in combination with FOLFOX, or as a single agent in patients who have failed oxaliplatin- and irinotecan-based therapy and who are intolerant to irinotecan.
Erbitux is contraindicated in combination with oxaliplatin-containing chemotherapy in patients with mutant RAS mCRC or for whom RAS mCRC status is unknown.
Erbitux is a highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor. As a monoclonal antibody, the mode of action of Erbitux is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites.
Merck licensed the right to market Erbitux outside the U.S. and Canada from ImClone LLC, a wholly-owned subsidiary of Eli Lilly and Company, in 1998. In Japan, ImClone, Bristol-Myers Squibb Company and Merck jointly develop and commercialize Erbitux. Merck has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas.
