The RAISE trial (NCT01183780) demonstrated that RAM plus FOLFIRI (leucovorin, fluorouracil, and irinotecan) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus FOLFIRI (PBO) as second-line mCRC treatment. Despite multiple approved anticancer treatments targeting angiogenesis, there are currently no predictive markers to guide patient selection. The extensive RAISE biomarker program assessed the association of multiple candidate biomarkers with RAM efficacy outcomes.
Plasma and tumor tissue collection was mandatory in the RAISE trial. Analyses were performed using exploratory assays to assess the correlations of the baseline marker levels (vascular endothelial growth factor [VEGF]-C and D; soluble vascular endothelial growth factor receptor [sVEGFR]1, 2, and 3; and VEGFR2 immunohistochemistry in tumor tissue) with clinical outcomes. Cox regression analyses adjusted for stratification factors were performed for each marker.
Biomarker results were available from >80% of patients. Among the candidate biomarkers analyzed, only VEGF-D levels had a consistent and statistically significant association with OS and PFS, suggesting a predictive relationship. Higher levels were associated with improved RAM efficacy (Table). This relationship was consistent across the full range of VEGF-D levels.Table:
555P Correlation of VEGF-D with Efficacy Outcomes: based on cut point from exploratory subset. Results below from combined exploratory + confirmatory groups
|Prespecified cut point||≥115 pg/mL|
These analyses from RAISE identified VEGF-D as a potential predictive marker for RAM efficacy in mCRC. Further investigation of this relationship is being pursued.
Clinical trial identification
Legal entity responsible for the study
Eli Lilly and Company
Eli Lilly and Company
J. Tabernero: Consultant/advisory board roles for Amgen, Bayer, Boehringer Ingelheim, Celgene, Chugai, Eli Lilly and Company, Imclone, Merck Serono, MSD, Novartis, Pfizer, Roche, Sanofi, Symphogen, and Taiho. R.R. Hozak: Employee and stockholder of Eli Lilly and Company. T. Yoshino: Research funding from GlaxoSmithKline K.K. and Boehringer Ingelheim GmbH. A.L. Cohn: Speaker’s bureau for Merrimack and consultant for BMS and Genentech. R. Obermannova: Consultant for Amgen, Roche, and Bayer; on the speaker’s bureau for Amgen, Roche, and Eli Lilly and Company; research funding from Merck. T-E. Ciuleanu: Advisory role for Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Ipsen, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, Serono, Servier and Teva. D.C. Portnoy: Consultant for Eli Lilly and Company. K. Muro: Corporate-sponsored research for Shionogi & Co Ltd., MSD KK, Daiichi Sankyo Co Ltd, and Gilead Sciences and honoraria for lectures for Chugai, Takeda, Taiho, Merck Serono, Eli Lilly Japan, and Yakult Honsha. H. Ouyang: Former employee and current stockholder of Eli Lilly and Company. S. Melemed: Employee and stockholder of Eli Lilly and Company. D. Ferry: Employee and stockholder of Eli Lilly and Company. F. Nasroulah: Full-time employee of Eli Lilly and Company. E. Van Cutsem: Research grants and advisor for Amgen, Bayer, Boehringer, Celgene, Eli Lilly and Company, Ipsen, Merck, Merckserono, Novartis, Roche, Sanofi, and Servier. All other authors have declared no conflicts of interest.