138411-158

RAISE: A randomized, double-blind, multicenter phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab (RAM) or placebo (PBO) in patients (pts) with metastatic colorectal carcinoma (CRC) progressive during or following first-line combination therapy with bevacizumab (bev), oxaliplatin (ox), and a fluoropyrimidine (fp).

Category: 
Cancers of the Colon, Rectum, and Anus
Session Type and Session Title: 
Oral Abstract Session: Cancers of the Colon, Rectum, and Anus
General Poster Session C: Cancers of the Colon, Rectum, and Anus
Abstract Number: 

512

Poster Board Number: 
General Poster Session C (Board #A6)
Citation: 
J Clin Oncol 33, 2015 (suppl 3; abstr 512)
Author(s): 
Josep Tabernero, Allen Lee Cohn, Radka Obermannova, Gyorgy Bodoky, Rocio Garcia-Carbonero, Tudor-Eliade Ciuleanu, David Craig Portnoy, Eric Van Cutsem, Axel Grothey, Jana Prausová, Pilar Garcia-Alfonso, Kentaro Yamazaki, Philip R. Clingan, Vittorina Zagonel, Tae Won Kim, Lorinda Simms, Shao-Chun Chang, Federico Nasroulah, Takayuki Yoshino, The RAISE Study Investigators; Vall d'Hebron University Hospital, Barcelona, Spain; Rocky Mountain Cancer Centers, US Oncology, Denver, CO; Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic; Szent László Hospital, Budapest, Hungary; Hospital Virgen del Rocio, Sevilla, Spain; Prof. Dr. I. Chiricuta Institute of Oncology, Cluj County, Romania; The West Clinic, Memphis, TN; University Hospitals Gasthuisberg/Leuven, Leuven, Belgium; Mayo Clinic, Rochester, MN, Rochester, MN; University Hospital Motol, Prague, Czech Republic; Hospital General Universitario Gregorio Marañón, Madrid, Spain; Shizuoka Cancer Center, Shizuoka, Japan; Southern Medical Day Care Centre, Wollongong, Australia; Oncologia Medica I, Istituto Oncologico Veneto, IRCCS, Padova, Italy; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Eli Lilly Canada Inc., Toronto, ON, Canada; Eli Lilly and Company, Indianapolis, IN; Eli Lilly and Company, Bridgewater, NJ; National Cancer Center Hospital East, Kashiwa, Japan

Abstract Disclosures

Abstract: 

Background: Angiogenesis is an important therapeutic target in CRC; VEGF plays a key role in angiogenesis. RAM is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. The RAISE study evaluated the efficacy and safety of adding RAM to standard second-line treatment FOLFIRI. Methods: Eligible pts with mCRC who progressed on or after first-line combination therapy with bev, ox, and fp, had an ECOG PS of 0 or 1, and adequate organ function were randomized 1:1 (stratified by region, KRAS mutation status, and time to progressive disease [PD] after beginning first-line treatment) to receive RAM (8 mg/kg IV) plus FOLFIRI or PBO plus FOLFIRI every 2 weeks until PD, unacceptable toxicity, or death. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Planned sample size of 1,050 pts ensured 85% power to demonstrate statistical significance at an overall two-sided alpha of 0.05, assuming a hazard ratio (HR) of 0.8. Results: Between Dec 2010 and Aug 2013, 1,072 eligible pts were randomized (RAM 536; PBO 536). Baseline pt characteristics were similar between treatment arms. The OS HR was 0.84 (95% CI: 0.73, 0.98; log-rank p=0.0219). Median OS was 13.3months (m) for RAM vs 11.7m for PBO. The PFS HR was 0.79 (95% CI: 0.70, 0.90; log-rank p = 0.0005). Median PFS with RAM was 5.7m and 4.5m for PBO. ORR was 13.4% RAM; 12.5% PBO (p = 0.6336). Subgroup results were consistent with the OS and PFS results. Grade ≥3 adverse events (AEs) occurring in >5% of pts in RAM+FOLFIRI were: neutropenia (RAM 38.4% vs PBO 23.3% ), hypertension (11.2% vs 2.8%), diarrhea (10.8% vs 9.7%), and fatigue (11.5% vs 7.8%). Conclusions: RAISE met its primary end-point, demonstrating a statistically significant improvement in OS for RAM and FOLFIRI vs PBO and FOLFIRI in second-line mCRC pts. Benefits were similar across important clinical subgroups and no unexpected AEs were identified. Clinical trial information: NCT01183780