Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 25, No 18S (June 20 Supplement), 2007: 4000
© 2007 American Society of Clinical Oncology

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Abstract

Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial

University Hospital Gasthuisberg/Leuven, Leuven, Belgium; Klinika Nowotworow Jelita Grubego, Warsaw, Poland; Orszagos Onkologiai Intézet, Budapest, Hungary; Ospedale di Torrette, Ancona, Italy; National Medical University, Kiev, Ukraine; Hospital Clinic i Provincial de Barcelona, Barcelona, Spain; Hôpital Ambroise Paré, Boulogne, France; The Royal Marsden Hospital, London, United Kingdom; Merck KGaA, Darmstadt, Germany; Klinikum Oldenburg GmbH, Oldenburg, Germany

4000

Background: Cetuximab in combination with irinotecan-based regimens has proven activity in previously-treated patients (pts) with mCRC. The present trial investigated the effectiveness of cetuximab in combination with standard FOLFIRI compared with FOLFIRI alone in the first-line treatment of pts with epidermal growth factor receptor (EGFR)-expressing mCRC. Methods: Pts were randomized 1:1 to receive either cetuximab (400 mg/m² initial dose then 250 mg/m²/week [w]) plus FOLFIRI q 2 w (irinotecan 180 mg/m², FA 400 mg/m², 5-FU bolus 400 mg/m², 5-FU infusion 2,400 mg/m² over 46 hours) (Group A) or FOLFIRI alone (Group B). The primary endpoint was progression-free survival (PFS), with secondary endpoints of overall survival (OS), response rate (RR), disease control rate and safety. 633 events were required to statistically differentiate PFS between groups with 80% power. Results: Between August 2004 and October 2005, 1,217 pts were randomized, 608 to Group A and 609 to Group B (60% male, median age 61 [19–84], ECOG performance status: 0=54%; 1=43.5%; 2=3.5%). Median PFS was significantly longer for Group A compared to Group B (8,9 months [8 - 9,5] for Group A vs. 8 months [7.6 - 9] for Group B, p=0.036). Response Rate was also significantly increased by cetuximab (46.9% vs. 38.7%, p=0.005). Treatment was generally well tolerated with neutropenia (26.7% Group A, 23.3% Group B), diarrhea (15.2% and 10.5% respectively) and skin reactions (18.7% and 0.2% respectively) being the most common grade 3/4 adverse events. Conclusions: Cetuximab in combination with FOLFIRI significantly increases response rate and significantly prolongs PFS in the first-line treatment of pts with mCRC, reducing the relative risk of progression by approximately 15%. Treatment-related side effects of cetuximab in combination with FOLFIRI were as expected, with diarrhea being moderately and skin reactions significantly more frequent as compared to FOLFIRI alone.

Author Disclosure

Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck KGaA Merck, Pfizer Merck, Pfizer Merck, Pfizer

Abstract presentation from the 2007 ASCO Annual Meeting