Adding the antiangiogenic antibody ramucirumab to second-line therapy for metastatic colorectal cancer improves outcomes with acceptable toxicity, according to results of a randomized, phase III trial that will be reported this week at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.
Researchers led by Dr. Josep Tabernero, director of the Vall d’Hebron Institute of Oncology in Barcelona, enrolled 1,072 patients with metastatic colorectal cancer that had progressed after receipt of first-line therapy containing bevacizumab (Avastin).
Courtesy of the American Society of Clinical Oncology
Dr. Josep Tabernero
They randomized the patients evenly to receive FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) chemotherapy plus either placebo or ramucirumab (Cyramza), an antibody to vascular endothelial growth factor receptor 2 (VEGFR-2) that is approved by the Food and Drug Administration for treatment of advanced stomach, gastroesophageal junction, and non–small cell lung cancers.
Main results showed that relative to the placebo group, the ramucirumab group had superior overall survival (median 13.3 vs. 11.7 months; hazard ratio, 0.84; P = .022), the primary endpoint, and progression-free survival (median 5.7 vs. 4.5 months; HR, 0.79; P = .0005).
The survival benefit was similar across patients stratified by various clinical and disease factors, including tumor KRAS mutational status and time to progression after first-line therapy, Dr. Tabernero reported.
Patients in the ramucirumab group had higher rates of certain grade 3 and 4 adverse events, most commonly neutropenia, fatigue, diarrhea, and hypertension. But the rate of febrile neutropenia was similar for the ramucirumab and placebo groups (3.6% vs. 2.7%).
The trial, known as 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), was sponsored by Eli Lilly and Company.