Cetuximab (C225) alone or in combination with irinotecan (CPT-11) in patients with epidermal growth factor receptor (EGFR)-positive, irinotecan-refractory metastatic colorectal cancer (MCRC).

Category: Lower Gastrointestinal Cancer

Authors: D. Cunningham, Y. Humblet, S. Siena, D. Khayat, H. Bleiberg, A. Santoro, D. Bets, M. Mueser, A. Harstrick, E. Van Cutsem; The Royal Marsden Hosp, Sutton, UK; St.Luc University Hospital, Brussels, Belgium; Ospedale Niguarda Ca' Granda, Milan, Italy; Hospital Pitie-Salpetriere, Paris, France; Institut Jules-Bordet, Brussels, Belgium; Istituto Clinico Humanitas, Rozzano, Italy; Merck Nederland B.V., Amsterdam, Netherlands; Merck KGaA, Darmstadt, Germany; University Hospital Gasthuisberg, Leuven, Belgium

Abstract:Cetuximab is a chimeric anti-EGFR monoclonal antibody with efficacy against MCRC previously treated with irinotecan-based chemotherapy (Saltz et al: Proc ASCO 2001and 2002). The current trial was designed to determine the objective confirmed response rate of the combination of cetuximab plus irinotecan, or of cetuximab as a single agent in patients with EGFR-positive, irinotecan-refractory MCRC. Secondary endpoints included: time to progression and survival time. Of 576 patients screened, 470 were EGFR-positive (82%). 329 patients were randomized in a 2:1 ratio. Patients in arm A received cetuximab (400 mg/m² 1st infusion, then 250 mg/m² weekly) plus irinotecan at the same dose and schedule on which they had been progressing. Patients in arm B received cetuximab alone with the option to switch to the combination of cetuximab with irinotecan after failure of cetuximab as a single agent. 218 patients were accrued in arm A (75 female, 143 male, median age 71, 88% with KPS 80 - 100) and 111 in arm B (46 female, 65 male, median age 70, 85% with KPS 80 - 100). 211 serious adverse events were observed. 65 (31%) were considered at least possibly related to the study medication, but were consistent with the known safety profiles of irinotecan and cetuximab. Preliminary evaluation is based on investigator assessment. Arm A response rate 17.9 % (95 % CI 13.0 - 27.7 %), median TTP 126 days (95 % CI 88 -131 d); arm B response rate 9.9 % (95 % CI 5.0 - 17.1 %), median TTP 45 days (95 % CI 43 - 84 d). A blinded independent read of all pretreatment and on study CT scans is ongoing and will be available together with the survival data for the meeting.