541P - Folfiri Plus Cetuximab in Patients with Liver-Limited or Non-Liver-Limited Ras Wild-Type Metastatic Disease: a Sub-Group Analysis of the Crystal Study

Abstract

ABSTRACT Aim: In the CRYSTAL study, adding cetuximab (cet) to first-line chemotherapy (CT) improved clinical outcome in patients (pts) with RAS (KRAS exons 2, 3 and 4 and NRAS exons 2, 3 and 4) wild-type (wt) metastatic colorectal cancer. A retrospective sub-group analysis investigated the benefit of treatment according to whether pts had liver-limited disease (LLD) or non-LLD in this patient group with RAS wt tumors. Methods: Cox's proportional hazards models for overall survival (OS) and progression-free survival (PFS) or Cochran-Mantel-Haenszel tests for objective response (ORR) and R0 resection were used on individual pt data. Results: Data for 367 RAS wt CRYSTAL study pts were analyzed. Adding cet to CT significantly improved PFS, and ORR in both LLD and non-LLD pts with RAS wt disease compared with CT alone (table). An improvement in OS and R0 resection rate was also observed for the addition of cet to CT in both LLD and non-LLD pts (table). Treatment effects also varied by LLD status: for OS, hazard ratio (HR) = 0.65 for LLD vs HR = 0.71 for non-LLD, for PFS, HR = 0.21 for LLD vs HR = 0.65 for non-LLD and for R0 resection the odds ratios were 2.68 for LLD and 5.94 for non-LLD. RAS wt pts (n = 367) LLD Non-LLD CT CT + cet CT CT + cet (n = 46) (n = 43) (n = 143) (n = 135) OS Median, mo 29.5 29.8 17.4 27.1 HR [95%CI] 0.65 [0.38, 1.10] 0.71 [0.54, 0.93] p 0.1069 0.0118 PFS Median, mo 8.1 14.0 8.5 11.2 HR [95%CI] 0.21 [0.09, 0.49] 0.65 [0.46, 0.93] p 0.0001 0.0156 Response ORR % 37.0 83.7 39.2 60.7 Odds ratio [95%CI] 8.99 [3.17, 25.52] 2.44 [1.49, 3.98] p 0.0003 R0 resection Rate % 6.5 16.3 0.7 4.4 Odds ratio [95%CI] 2.68 [0.63, 11.43] 5.94 [0.79, 44.88] p 0.1791 0.0400 Conclusions: In pts with RAS wt tumors, a significant clinical benefit was seen from the addition of cet to CT for PFS and ORR in both LLD and non-LLD pts but with a better absolute treatment outcome observed in LLD pts. In both LLD and non-LLD pts the addition of cet to CT increased the R0 resection rate and reduced the risk of death but the difference was only significant for those pts with non-LLD. The small pt numbers preclude drawing any meaningful conclusion from this observation. The selection of pts on the basis of an expanded analysis of their RAS wt disease status improves the clinical outcome benefits when compared with those for pts with KRAS codon 12/13 wt LLD or non-LLD (Kohne at al., ASCO 2011, abstr 3576). Disclosure: C. Kohne: Honoraria for lectures from Merck, Amgen, Pfizer, Sanofi, Bayer Collaboration in clinical trials for Roche, Novartis, Pfizer, Bayer, Merck; G. Folprecht: Honoraria for lectures and advisory boards (Merck), study grant (Merck); F. Ciardiello: Participation to Advisory Boards and Satellite Symposia: Merck Serono, Bayer, Roche, Astellas, Lilly Research funding: Bayer, AstraZeneca; P. Ronga: Philippe Ronga is an employee of Merck KGaA, Darmstadt, Germany; F. Beier: Employee of Merck KGaA, Germany; E. Van Cutsem: Eric Van Cutsem has received research funding from Merckserono paid to his institution.