Web of Science: 51 cites, Scopus: 51 cites, Google Scholar: cites,
Analysis of angiogenesis biomarkers for ramucirumab efficacy in patients with metastatic colorectal cancer from RAISE, a global, randomized, double-blind, phase III study
Tabernero, J (Hospital Universitari Vall d'Hebron)
Hozak, R R (Oncology, Eli Lilly and Company, Indianapolis, USA)
Yoshino, T (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 (Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic)
Bodoky, G (Oncology, Szent László Hospital, Budapest, Hungary)
Garcia-Carbonero, R (CIBERONC, Universidad Complutense, Madrid, Spain)
Ciuleanu, T -E (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 (Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan)
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, S A (Oncology, Eli Lilly and Company, Indianapolis, USA)
Ferry, D (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. Creative Commons
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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