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.
|Number of pages||10|
|Journal||European Journal of Cancer|
|Publication status||Published - 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