Analysis of angiogenesis biomarkers for ramucirumab efficacy in patients with metastatic colorectal cancer from RAISE, a global, randomized, double-blind, phase III study
Tabernero, Josep (Hospital Universitari Vall d'Hebron)
Hozak, Rebecca R (Oncology, Eli Lilly and Company, Indianapolis, USA)
Yoshino, Takayuki (Division of Gastrointestinal Oncology/Digestive Endoscopy, National Cancer Center Hospital East, Chiba, Japan)
Cohn, A. L. (Medical Oncology, Rocky Mountain Cancer Center/US Oncology, Denver, USA)
Obermannova, R. (Masaryk Memorial Cancer Institute (Brno, República Txeca))
Bodoky, G. (St László Hospital (Hongria))
García-Carbonero, Rocío (Universidad Complutense de Madrid)
Ciuleanu, Tudor Eliade (Medical Oncology, Prof. Dr. I. Chiricuţă Institute of Oncology, Cluj-Napoca, Romania)
Portnoy, D. C. (Oncology, West Clinic, Memphis, USA)
Prausová, J. (Department of Oncology and Radiotherapy, University Hospital Motol, Prague, Czech Republic)
Muro, K. (Aichi Cancer Center Hospital)
Siegel, R. W. (Laboratory for Experimental Medicine, Eli Lilly and Company, Indianapolis, USA)
Konrad, R. J. (Laboratory for Experimental Medicine, Eli Lilly and Company, Indianapolis, USA)
Ouyang, H. (Oncology, Eli Lilly and Company, Indianapolis, USA)
Melemed, Symantha A (Oncology, Eli Lilly and Company, Indianapolis, USA)
Ferry, David (Oncology, Eli Lilly and Company, Indianapolis, USA)
Nasroulah, F. (Oncology, Eli Lilly and Company, Argentina)
Van Cutsem, E. (KU Leuven, Leuven, Belgium)
Universitat Autònoma de Barcelona

Data:	2017
Resum:	The phase III RAISE trial (NCT01183780) demonstrated that the vascular endothelial growth factor (VEGF) receptor (VEGFR)-2 binding monoclonal antibody ramucirumab plus 5-fluororuracil, leucovorin, and irinotecan (FOLFIRI) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo + FOLFIRI as second-line metastatic colorectal cancer (mCRC) treatment. To identify patients who benefit the most from VEGFR-2 blockade, the RAISE trial design included a prospective and comprehensive biomarker program that assessed the association of biomarkers with ramucirumab efficacy outcomes. Plasma and tumor tissue collection was mandatory. Overall, 1072 patients were randomized 1 : 1 to the addition of ramucirumab or placebo to FOLFIRI chemotherapy. Patients were then randomized 1 : 2, for the biomarker program, to marker exploratory (ME) and marker confirmatory (MC) groups. Analyses were carried out using exploratory assays to assess the correlations of baseline marker levels [VEGF-C, VEGF-D, sVEGFR-1, sVEGFR-2, sVEGFR-3 (plasma), and VEGFR-2 (tumor tissue)] with clinical outcomes. Cox regression analyses were carried out for each candidate biomarker with stratification factor adjustment. Biomarker results were available from >80% (n = 894) of patients. Analysis of the ME subset determined a VEGF-D level of 115 pg/ml was appropriate for high/low subgroup analyses. Evaluation of the combined ME + MC populations found that the median OS in the ramucirumab + FOLFIRI arm compared with placebo + FOLFIRI showed an improvement of 2. 4 months in the high VEGF-D subgroup [13. 9 months (95% CI 12. 5–15. 6) versus 11. 5 months (95% CI 10. 1–12. 4), respectively], and a decrease of 0. 5 month in the low VEGF-D subgroup [12. 6 months (95% CI 10. 7–14. 0) versus 13. 1 months (95% CI 11. 8–17. 0), respectively]. PFS results were consistent with OS. No trends were evident with the other antiangiogenic candidate biomarkers. The RAISE biomarker program identified VEGF-D as a potential predictive biomarker for ramucirumab efficacy in second-line mCRC. Development of an assay appropriate for testing in clinical practice is currently ongoing. NCT01183780.
Drets:	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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Ramucirumab ; Colorectal cancer ; VEGF-D ; Viomarkers ; Predictive
Publicat a:	Annals of oncology, Vol. 29 (december 2017) , p. 602-609, ISSN 1569-8041

DOI: 10.1093/annonc/mdx767
PMID: 29228087

8 p, 590.0 KB

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