Efficacy of cetuximab immediately after bevacizumab: A phase III multicenter trial comparing two different sequences of cetuximab and FOLFOX in K-Ras WT metastatic colorectal cancer patients refractory FOLFIRI/bevacizumab

• Published in: Journal of clinical oncology Vol. 34; no. 4_suppl; p. 632
• Main Authors: Cascinu, Stefano, Zaniboni, Alberto, Lonardi, Sara, Rosati, Gerardo, Nasti, Guglielmo, Giordano, Monica, Corsi, Domenico C., Ferraú, Francesco, Iaffaioli, Rosario Vincenz, Marchetti, Paolo, Aglietta, Massimo, Bilancia, Domenico, Ronzoni, Monica, Floriani, Irene Claudia, Labianca, Roberto
• Format: Journal Article
• Language: English
• Published: 01.02.2016
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2016.34.4_suppl.632

Abstract only 632 Background: FOLFOX/FOLFIRI are effective as first-line treatment but FOLFOX might be more effective in second line. The optimal first-line in RAS wild type mCRC is still unclear even after 2 trials comparing chemotherapy with bevacizumab or cetuximab. While bevacizumab seems to loose efficacy across treatment lines, cetuximab has a similar activity across all treatment lines. It might be a better choice for the third-line in the view of an optimal sequence strategy. We designed a phase III randomised trial to compare two different treatment sequences of cetuximab and FOLFOX in mCRC patients refractory to FOLFIRI/bevacizumab first-line. Methods: Pts were randomized to receive Irinotecan/Cetuximab as 2 nd line followed by FOLFOX-4 as 3 rd line (Arm A) or the inverse sequence. Primary endpoint was progression free survival (PFS); secondary endpoints were overall survival and toxicity. 101 events were required in order to detect an hazard ratio of 0.57, translating in an increase of median PFS from 4 to 7 months (two-sided type I error 5%, power 80%). Results: 110 mCC pts were enrolled in this trial: 64 pts were males and 46 females with a mean age of 61 years. Efficacy results are reported in the table. Treatment was well tolerated with a low number of serious adverse reactions (2 in each treatment arm). Conclusions: Cetuximab is less effective immediately after bevacizumab. This is in accordance with data suggesting that EGFR inhibition is not active after VEGF blockade. The sequence of biological agents seems to be more relevant than the first-line choice. In RAS wild type patients progressing after a first line bevacizumab based therapy cetuximab should be given as first line or third line. Clinical trial information: NCT01030042. [Table: see text]