Cetuximab with irinotecan in first-line treatment of epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer (mCRC): Preliminary safety results (CRYSTAL)

Abstract

3555 Background: Cetuximab is an IgG1 monoclonal antibody targeting the EGFR with proven activity in previously treated mCRC patients (pts). The modified two-weekly de Gramont regimen of irinotecan with infusional 5-fluorouracil (5-FU)/folinic acid (FA) (FOLFIRI) is a standard for metastatic disease. This randomized trial investigates the effectiveness of cetuximab with this chemotherapy combination versus chemotherapy alone in (pts) with EGFR-expressing mCRC previously untreated for metastatic disease. Methods: This phase III trial compares cetuximab (400 mg/m2 week 1 then 250 mg/m2 weekly) added to FOLFIRI (irinotecan 180 mg/m2, FA 400 mg/m2, 5-FU bolus 400 mg/m2, 2400 mg/m2 infusional 5-FU) (group A) vs. FOLFIRI alone (group B) in pts with EGFR-detectable tumors. 1080 pts are planned to detect a difference of ≥ 2 months in PFS with 80% power. The Data Safety Monitoring Board (DSMB) has performed an independent preplanned safety evaluation of 401 treated pts. Results: Pts (M/F 252/149, median age 62 years [range, 19–84], ECOG performance status [PS]: PS0, 57.1%: PS1, 38.4%: PS2, 4.5%) received at least 3 treatment cycles to date. Of the 401 pts, 83 (20.7%) pts completed/discontinued the trial. There were 11 deaths (2.7%) within 30 days of the last study treatment: 5 related to disease, 3 to chemotherapy, and 3 other (2 unknown, 1 intercurrent illness). Most common adverse events of the pooled safety data were skin reactions, diarrhea and nausea. Conclusions: After review of all relevant safety information by the DSMB, the trial continues. Recruitment was completed with 1220 patients in December 2005. [Table: see text] [Table: see text]