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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 Yoshino, T. Portnoy, D. C. Obermannova, Radka Bodoky, György Prausová, J. Tabernero Caturla, Josep Garcia-Carbonero, Rocio Institut Català de la Salut [Yoshino T] National Cancer Center Hospital East, Kashiwa, Japan. [Portnoy DC] The West Clinic, Memphis, USA. [Obermannová R] Masarykuv Onkologicky Ustav, Brno, Czech Republic. [Bodoky G] St. Laszlo Hospital, Budapest, Hungary. [Prausová J] Fakultni Nemocnice v MOTOLE, Prague, Czech Republic. [Garcia-Carbonero R] Hospital Hospital Universitario Doce de Octubre, IIS imas12, UCM, CNIO, CIBERONC, Madrid, Spain. [Tabernero J] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. CIBERONC, Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus Còlon - Càncer Recte - Càncer Marcadors tumorals DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Metastasis CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor Other subheadings::Other subheadings::/analysis ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales ENFERMEDADES::neoplasias::procesos neoplásicos::metástasis neoplásica COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales Otros calificadores::Otros calificadores::/análisis Carcinoma colorrectal; Ramucirumab; BRAF Carcinoma colorrectal; Ramucirumab; BRAF Colorectal carcinoma; Ramucirumab; BRAF 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. This work was supported by Eli Lilly and Company. No grant number is applicable. 2021-03-19T12:39:55Z 2021-03-19T12:39:55Z 2018 2019-01-01 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Yoshino T, Portnoy DC, Obermannová R, Bodoky G, Prausová J, Garcia-Carbonero R, et al. 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. Ann Oncol. 2019;30(1):124–31. 1569-8041 https://hdl.handle.net/11351/5778 10.1093/annonc/mdy461 30339194 000459677700018 http://hdl.handle.net/11351/5778 eng Annals of Oncology;30 https://www.sciencedirect.com/science/article/pii/S0923753419309792 Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess application/pdf Oxford University Press Scientia