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. (September 2017)

• Record Type: Journal Article
• Authors: Cascinu, Stefano; Rosati, Gerardo; Nasti, Guglielmo; Lonardi, Sara; Zaniboni, Alberto; Marchetti, Paolo; Leone, Francesco; Bilancia, Domenico; Iaffaioli, Rosario Vincenzo; Zagonel, Vittorina; Giordano, Monica; Corsi, Domenico C.; Ferraú, Francesco; Labianca, Roberto; Ronzoni, Monica; Scartozzi, Mario; Galli, Francesca
• Is Part Of: European journal of cancer. Volume 83(2017)
• Page Start: 106
• Page End: 115
• Publication Date: 2017-09
• Subjects: Metastatic colorectal cancer -- Treatment strategy -- K-RAS wild type -- Cetuximab -- Treatment sequence; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2017.06.029
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: 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. Highlights: The effect of introducing in second or third-line cetuximab after a progression to FOLFIRI/bevacizumab. No difference in progression-free survival among the two sequences. A trend for a better overall survival for cetuximab third-line. An observed reduced activity of cetuximab after a first-line bevacizumab-based therapy. This reduced activity may have relevant therapeutic consequences in patients with left tumours.