Analysis of angiogenesis biomarkers for ramucirumab efficacy in patients with metastatic colorectal cancer from RAISE, a global, randomized, double-blind, phase III study.

Autor:	Tabernero J; Medical Oncology, Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Barcelona, Spain; CIBERONC, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: jtabernero@vhio.net., Hozak RR; Oncology, Eli Lilly and Company, Indianapolis, USA., Yoshino T; Division of Gastrointestinal Oncology/Digestive Endoscopy, National Cancer Center Hospital East, Chiba, Japan., Cohn AL; 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; Medical Oncology Department, Hospital Universitario 12 de Octubre, CNIO; CIBERONC, Universidad Complutense, Madrid, Spain., Ciuleanu TE; Medical Oncology, Prof. Dr. I. Chiricuţă Institute of Oncology, Cluj-Napoca, Romania., Portnoy DC; 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 RW; Laboratory for Experimental Medicine, Eli Lilly and Company, Indianapolis, USA., Konrad RJ; Laboratory for Experimental Medicine, Eli Lilly and Company, Indianapolis, USA., Ouyang H; Oncology, Eli Lilly and Company, Indianapolis, USA., Melemed SA; 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; Digestive Oncology, University Hospital Gasthuisberg, Leuven, Belgium; KU Leuven, Leuven, Belgium.
Jazyk:	angličtina
Zdroj:	Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2018 Mar 01; Vol. 29 (3), pp. 602-609.
DOI:	10.1093/annonc/mdx767
Abstrakt:	Background: 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. Patients and Methods: 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. Results: 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. Conclusions: 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. Clinical Trials Registration: NCT01183780.
Databáze:	MEDLINE
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