The RAISE trial met its primary endpoint. The addition of ramucirumab induced an increase in overall survival, with a hazard ratio of 0.84.
—Josep Tabernero, MD, PhD
The phase III international RAISE trial found that ramucirumab (Cyramza) extends survival when given with chemotherapy to metastatic colorectal cancer patients who progress on treatment,1 but some experts commented that “financial toxicity” might be an issue, given the modest benefit.
“The RAISE trial met its primary endpoint. The addition of ramucirumab induced an increase in overall survival, with a hazard ratio [HR] of 0.84. The addition of ramucirumab also significantly increased progression-free survival,” said Josep Tabernero, MD, PhD, Head of Medical Oncology at Vall d’Hebron University Hospital and Director of the Vall d’Hebron Institute of Oncology in Barcelona.
Ramucirumab is a fully human monoclonal antibody that inhibits angiogenesis by targeting the vascular endothelial growth factor (VEGF) receptor 2 and prevents binding of VEGF. It was approved by the U.S. Food and Drug Administration in 2014 to treat gastric or gastroesophageal junction cancer and non–small cell lung cancer following progression.
The RAISE study randomly assigned 1,072 patients to second-line treatment with FOLFIRI (leucovorin, fluorouracil, irinotecan) plus ramucirumab or placebo. Patients had shown disease progression during or following first-line combination therapy with bevacizumab (Avastin), oxaliplatin, and a fluoropyrimidine.
The response rates were similar between the two arms—13.4% with ramucirumab; 12.5% with placebo—but ramucirumab significantly improved both progression-free and overall survival.
All Subgroups Benefited
Median time to disease progression in patients receiving ramucirumab plus FOLFIRI was 5.7 months compared with 4.5 months in the placebo arm (HR = 0.79, P = .0005). Median overall survival was 13.3 months and 11.7 months (HR = 0.84, P = .0219), respectively.
“All different subgroups benefited in terms of overall survival, and there was even more consistent benefit in progression-free survival,” he said. The arms were balanced for the proportion of patients (> 50%) receiving post-treatment regimens and the particular agents they received, he added.
Treatment with ramucirumab plus FOLFIRI was well tolerated, though the addition of ramucirumab increased the incidence of grade 3/4 neutropenia, fatigue, diarrhea, and hypertension.
“Though the rate of neutropenia was higher, the rate of febrile neutropenia, the clinically significant toxicity, was similar—3.6% vs 2.7% in the placebo arm,” said Dr. Tabernero, “and the adverse events were manageable.”
The study validates angiogenesis as an important target in colorectal cancer, he said. Other antiangiogenic agents approved in this malignancy include bevacizumab, ziv-aflibercept (Zaltrap), and regorafenib (Stivarga).
Dr. Tabernero pointed out that the study population was representative of patients seen in everyday practice. He cautioned, however, that the findings should not be extrapolated to other regimens used in colorectal cancer. ■
Disclosure: Dr. Tabernero reported a consulting or advisory role with Amgen, Celgene, Chugai Pharma, ImClone Systems, Lilly, Merck KGaA, Millennium Takeda, Novartis, Roche/Genentech, Sanofi, and Taiho Pharmaceutical.
1. Tabernero J, Cohn AL, Obermannova R, et al: RAISE: A randomized, double-blind, multicenter phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab or placebo in patients with metastatic colorectal carcinoma progressive during or following first-line combination therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. 2015 Gastrointestinal Cancers Symposium. Abstract 512. Presented January 17, 2015.
I am writing in regard to the report and commentary in this issue on the RAISE Trial. To begin, a discussion of this phase III clinical trial presented at the 2015 Gastrointestinal Cancers Symposium (RAISE study) may not be the most appropriate forum to air legitimate views on finances and...
Commenting on the RAISE study at a press briefing held during the 2015 Gastrointestinal Cancers Symposium, moderator Smitha S. Krishnamurthi, MD, Associate Professor of Medicine at Case Western Reserve University School of Medicine, Cleveland, acknowledged that improvements of 1 to 2 months in...