Biomarker analysis beyond angiogenesis: RAS/RAF mutation status, tumour sidedness, and second-line ramucirumab efficacy in patients with metastatic colorectal carcinoma from RAISE—a global phase III study. (18th October 2018)

• Record Type: Journal Article
• Authors: Yoshino, T; Portnoy, D C; Obermannová, R; Bodoky, G; Prausová, J; Garcia-Carbonero, R; Ciuleanu, T; García-Alfonso, P; Cohn, A L; Van Cutsem, E; Yamazaki, K; Lonardi, S; Muro, K; Kim, T W; Yamaguchi, K; Grothey, A; O'Connor, J; Taieb, J; Wijayawardana, S R; Hozak, R R; Nasroulah, F; Tabernero, J
• Is Part Of: Annals of oncology. Volume 30:Number 1(2019)
• Page Start: 124
• Page End: 131
• Publication Date: 2018-10-18
• Subjects: colorectal carcinoma -- ramucirumab -- BRAF -- KRAS -- NRAS -- left; Oncology -- Periodicals; 616.992
• DOI: 10.1093/annonc/mdy461
• Languages: English
• ISSNs: 0923-7534

Abstract

Abstract: 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.