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, Takayuki (National Cancer Center Hospital East, Kashiwa, Japan)
Portnoy, D. C. (The West Clinic, Memphis, USA)
Obermannová, R. (Masarykuv Onkologicky Ustav, Brno, Czech Republic)
Bodoky, G. (St László Hospital (Hongria))
Prausová, J. (Fakultni Nemocnice v MOTOLE, Prague, Czech Republic)
García-Carbonero, Rocío (Hospital Universitario 12 de Octubre (Madrid))
Ciuleanu, Tudor Eliade (Institutul Oncologic Ion Chiricuta and UMF Iuliu Hatieganu, Cluj-Napoca, Romania)
García-Alfonso, Pilar (Hospital General Universitario Gregorio Marañón)
Cohn, A. L. (Rocky Mountain Cancer Center, LLP, Denver, USA)
Van Cutsem, E. (University Hospitals Gasthuisberg (Leuven, Bélgica))
Yamazaki, K. (Shizuoka Cancer Center, Shizuoka, Japan)
Lonardi, Sara (Istituto Oncologico Veneto-IRCCS, Padova, Italy)
Muro, K. (Aichi Cancer Center Hospital)
Kim, T. W. (Asan Medical Center, University of Ulsan, Seoul, Republic of Korea)
Yamaguchi, K. (The Cancer Institute Hospital of JFCR, Tokyo, Japan)
Grothey, A. (Mayo Clinic, Phoenix, USA)
O'Connor, J. (Instituto Alexander Fleming (Buenos Aires, Argentina))
Taieb, Julien (Sorbonne Paris Cité, Paris Descartes University, Georges Pompidou European Hospital, Paris, France)
Wijayawardana, S. R. (Eli Lilly and Company, Indianapolis, USA)
Hozak, Rebecca R (Eli Lilly and Company, Indianapolis, USA)
Nasroulah, F. (Eli Lilly and Company, Buenos Aires, Argentina)
Tabernero, Josep (Universitat Autònoma de Barcelona. Departament de Medicina)
Vall d'Hebron Institut d'Oncologia

Fecha:	2018
Resumen:	: 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. 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. 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). 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. NCT01183780.
Nota:	Altres ajuts: This work was supported by Eli Lilly and Company. No grant number is applicable.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Colorectal carcinoma ; Ramucirumab ; BRAF ; KRAS ; NRAS ; Left
Publicado en:	Annals of oncology, Vol. 30 (october 2018) , p. 124-131, ISSN 1569-8041

DOI: 10.1093/annonc/mdy461
PMID: 30339194

8 p, 712.6 KB

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