Treatment sequence with either irinotecan/cetuximab followed by FOLFOX-4 or the reverse strategy in metastatic colorectal cancer patients progressing after first-line FOLFIRI/bevacizumab: An Italian Group for the Study of Gastrointestinal Cancer phase III, randomised trial comparing two sequences of therapy in colorectal metastatic patients.

Stefano Cascinu, Gerardo Rosati, Guglielmo Nasti, Sara Lonardi, Alberto Zaniboni, Paolo Marchetti, Francesco Leone, Domenico Bilancia, Rosario Vincenzo Iaffaioli, Vittorina Zagonel, Monica Giordano, Domenico C. Corsi, Francesco Ferrau, Roberto Labianca, Monica Ronzoni, Mario Scartozzi, Francesca Galli

Research output: Contribution to journalArticle


INTRODUCTION: The optimal treatment strategy for RAS wild type (WT) mCRC is controversial. Our phase III study investigated the effect of introducing earlier (second-line) or later (third-line) cetuximab in patients progressed after FOLFIRI/bevacizumab first-line. PATIENTS AND METHODS: mCRC patients progressing after FOLFIRI/bevacizumab first-line were randomised to receive second-line irinotecan/cetuximab followed by third-line FOLFOX-4 (arm A) or the reverse sequence (arm B). Primary end-point was progression-free survival (PFS). RESULTS: About 54 and 56 patients were randomised in arm A and in arm B, respectively. After a median follow-up of 37.5 months, 100 PFS events were recorded. Median PFS was 9.9 months in arm A and 11.3 months in arm B (Hazard ratio [HR] 1.04, 95% confidence interval [CI]: 0.69-1.56, p = 0.854), while median overall survival was 12.3 months in arm A and 18.6 months in arm B (HR 0.84, 95% CI: 0.55-1.28; p = 0.411). No overall difference in side-effects were observed between the two treatment arms. CONCLUSIONS: This trial did not meet the primary end-point (PFS). Like other preclinical and clinical evidences, our study seems to suggest a reduced activity of cetuximab after a first-line bevacizumab-based therapy.
Original languageEnglish
Pages (from-to)106-115
Number of pages10
JournalEuropean Journal of Cancer
Publication statusPublished - Sep 1 2017



  • Aged, Antibodies, Monoclonal, Humanized/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use, Bevacizumab/administration & dosage, Camptothecin/administration & dosage/analogs & derivatives, Carcinoma/drug therapy, Cetuximab/administration & dosage, Colorectal Neoplasms/*drug therapy, Disease-Free Survival, Female, Fluorouracil/administration & dosage, Humans, Kaplan-Meier Estimate, Leucovorin/administration & dosage, Male, Middle Aged, Organoplatinum Compounds/administration & dosage, *Cetuximab, *K-RAS wild type, *Metastatic colorectal cancer, *Treatment sequence, *Treatment strategy

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