BACKGROUND: : Second-line treatment with ramucirumab+FOLFIRI improved overall survival (OS) versus placebo+FOLFIRI for patients with metastatic colorectal carcinoma (CRC) [hazard ratio (HR)=0.84, 95% CI 0.73-0.98, P = 0.022]. Post hoc analyses of RAISE patient data examined the association of RAS/RAF mutation status and the anatomical location of the primary CRC tumour (left versus right) with efficacy parameters. PATIENTS AND METHODS: Patient tumour tissue was classified as BRAF mutant, KRAS/NRAS (RAS) mutant, or RAS/BRAF wild-type. Left-CRC was defined as the splenic flexure, descending and sigmoid colon, and rectum; right-CRC included transverse, ascending colon, and cecum. RESULTS: RAS/RAF mutation status was available for 85% of patients (912/1072) and primary tumour location was known for 94.4% of patients (1012/1072). A favourable and comparable ramucirumab treatment effect was observed for patients with RAS mutations (OS HR = 0.86, 95% CI 0.71-1.04) and patients with RAS/BRAF wild-type tumours (OS HR = 0.86, 95% CI 0.64-1.14). Among the 41 patients with BRAF-mutated tumours, the ramucirumab benefit was more notable (OS HR = 0.54, 95% CI 0.25-1.13), although, as with the other genetic sub-group analyses, differences were not statistically significant. Progression-free survival (PFS) data followed the same trend. Treatment-by-mutation status interaction tests (OS P = 0.523, PFS P = 0.655) indicated that the ramucirumab benefit was not statistically different among the mutation sub-groups, although the small sample size of the BRAF group limited the analysis. Addition of ramucirumab to FOLFIRI improved left-CRC median OS by 2.5 month over placebo (HR = 0.81, 95% CI 0.68-0.97); median OS for ramucirumab-treated patients with right-CRC was 1.1 month over placebo (HR = 0.97, 95% CI 0.75-1.26). The treatment-by-sub-group interaction was not statistically significant for tumour sidedness (P = 0.276). CONCLUSIONS: In the RAISE study, the addition of ramucirumab to FOLFIRI improved patient outcomes, regardless of RAS/RAF mutation status, and tumour sidedness. Ramucirumab treatment provided a numerically substantial benefit in BRAF-mutated tumours, although the P-values were not statistically significant. CLINICALTRIALS.GOV NUMBER: NCT01183780.

Asan Medical Center University of Ulsan Seoul Republic of Korea

Department of Clinical Oncology Aichi Cancer Center Hospital Nagoya Japan

Eli Lilly and Company Buenos Aires Argentina

Eli Lilly and Company Indianapolis USA

Fakultni Nemocnice v MOTOLE Prague Czech Republic

Hospital General Univ Gregorio Marañón Madrid Spain

Hospital Universitario Doce de Octubre IIS imas12 UCM CNIO CIBERONC Madrid Spain

Instituto Alexander Fleming Buenos Aires Argentina

Institutul Oncologic Ion Chiricuta and UMF Iuliu Hatieganu Cluj Napoca Romania

Istituto Oncologico Veneto IRCCS Padova Italy

Masarykuv Onkologicky Ustav Brno Czech Republic

Mayo Clinic Phoenix USA

National Cancer Center Hospital East Kashiwa Japan

Rocky Mountain Cancer Center LLP Denver USA

Shizuoka Cancer Center Shizuoka Japan

Sorbonne Paris Cité Paris Descartes University Georges Pompidou European Hospital Paris France

St Laszlo Hospital Budapest Hungary

The Cancer Institute Hospital of JFCR Tokyo Japan

The West Clinic Memphis USA

Univ Hospital Gasthuisberg Leuven and KU Leuven Leuven Belgium

Vall d'Hebron University Hospital and Institute of Oncology Universitat Autònoma de Barcelona CIBERONC Barcelona Spain

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NCT01183780