An Open-Label Phase II Study Evaluating the Safety and Efficacy of Ramucirumab Combined With mFOLFOX-6 as First-Line Therapy for Metastatic Colorectal Cancer

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RESEARCH PRODUCT

An Open-Label Phase II Study Evaluating the Safety and Efficacy of Ramucirumab Combined With mFOLFOX-6 as First-Line Therapy for Metastatic Colorectal Cancer

Shaila Ballal Josep Tabernero Rocio Garcia-carbonero Jonathan D. Schwartz Joan Maurel Fernando Rivera Malcolm J. Moore Jean-pierre M. Ayoub Andrés Cervantes F. Nasroulah Timothy R. Asmis

subject

Vascular Endothelial Growth Factor A Cancer Research Pathology medicine.medical_specialty Organoplatinum Compounds Angiogenesis Colorectal cancer Leucovorin Antibodies Monoclonal Humanized Disease-Free Survival Drug Administration Schedule Ramucirumab chemistry.chemical_compound Antineoplastic Combined Chemotherapy Protocols medicine Humans Neoplasm Metastasis business.industry Clinical Trial Results Antibodies Monoclonal Kinase insert domain receptor medicine.disease Vascular Endothelial Growth Factor Receptor-2 Vascular endothelial growth factor Vascular endothelial growth factor A Treatment Outcome Oncology chemistry Fluorouracil Monoclonal Cancer research Fluorouracil business Colorectal Neoplasms medicine.drug Protein Binding

description

Abstract Author Summary Background. Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) are believed to mediate angiogenesis in colorectal cancer (CRC). Ramucirumab (RAM; IMC-1121B) is a human IgG1 monoclonal antibody that inhibits VEGF ligand binding to VEGFR-2, inhibiting VEGFR-2 activation and signaling. Methods. Patients with metastatic CRC, Eastern Cooperative Oncology Group performance status 0–1, and adequate organ function who had not received chemotherapy for metastatic disease received RAM and the modified FOLFOX-6 regimen every 2 weeks. Endpoints included progression-free survival (PFS), objective response rate, overall survival, and safety. The sample size was based on a potentially improved median PFS from 8 months to 11 months. Results. Forty-eight patients received therapy. Median PFS was 11.5 months (95% confidence interval [CI]: 8.6–13.1 months). The objective response rate was 58.3% (95% CI: 43.21–72.39). The disease control rate (complete or partial response plus stable disease) was 93.8% (95% CI: 82.8–98.7). Median overall survival was 20.4 months (95% CI: 18.5–25.1 months). The most frequent grade 3–4 adverse events included neutropenia (grade 3: 33.3%; grade 4: 8.3%), hypertension (grade 3: 16.7%), and neuropathy (grade 3: 12.5%). Two patients died during the study due to myocardial infarction and cardiopulmonary arrest. Conclusion. RAM may enhance the efficacy of modified FOLFOX-6 chemotherapy with an acceptable safety profile in metastatic CRC.

year	journal	country	edition	language
2014-03-27

http://hdl.handle.net/10550/44285