Spotlight on ramucirumab in the treatment of nonsmall cell lung cancer: design, development, and clinical activity

• Main Authors: Cobo M, Gutiérrez V, Villatoro R, Trigo JM, Ramos I, López O, Ruiz M, Godoy A, López I, Arroyo M
• Format: Article
• Language: English
• Published: Dove Medical Press 2017-07-01
• Series: Lung Cancer : Targets and Therapy
• Subjects: Ramucirumab; NSCLC; antiangiogenesis; VEGF-targeted therapy; second line therapy.
• Online Access: https://www.dovepress.com/spotlight-on-ramucirumab-in-the-treatment-of-nonsmall-cell-lung-cancer-peer-reviewed-article-LCTT

Manuel Cobo,1 Vanesa Gutiérrez,1 Rosa Villatoro,2 Jose Manuel Trigo,1 Inmaculada Ramos,1 Omar López,1 María Ruiz,1 Ana Godoy,1 Irene López,1 Macarena Arroyo3 1Medical Oncology Department, Hospital Universitario Málaga Regional y Virgen de la Victoria, IBIMA, 2Medical Oncology Department, Hospital Costa del Sol, Marbella, IBIMA, 3Pneumology Department, Hospital Universitario Málaga Regional, IBIMA, Málaga, Spain Abstract: The vascular endothelial growth factor (VEGF) and receptor is a therapeutic target because of the importance of this pathway in carcinogenesis. This pathway regulates and promotes angiogenesis as well as increases endothelial cell proliferation, permeability, and cancer survival. Ramucirumab is a new fully human monoclonal antibody that targets the VEGF receptor-2, an important key receptor implicated in angiogenesis. Ramucirumab has been approved for the treatment of second-line advanced or metastatic non-small cell lung cancer (NSCLC) in combination with the chemotherapy agent docetaxel. This was based on the result of the randomized trial REVEL of 1,253 patients with metastatic NSCLC previously treated with a platinum-based combination therapy. The authors observed a significant improvement in overall survival (OS) with an acceptable toxicities profile. In this study, patients were randomized to receive ramucirumab plus docetaxel or placebo with docetaxel. The combination of docetaxel and ramucirumab showed an improved OS (hazard ratio [HR]: 0.86; 95% CI: 0.75, 0.98). Median OS was 10.5 months in the ramucirumab arm versus 9.1 months in the placebo arm. Regarding side effects, the toxicity described on the ramucirumab arm were principally diarrhea, fatigue, and neutropenia. The most common (5%) adverse reactions of grade 3 and 4 in the ramucirumab arm were fatigue, neutropenia, febrile neutropenia, leukopenia, and hypertension. Adding ramucirumab to docetaxel improves QoL of patients, and does not impair symptoms or functioning. There are currently several trials in progress evaluating the effects of ramucirumab in combination with other drugs in patients with advanced NSCLC. Keywords: ramucirumab, NSCLC, antiangiogenesis, VEGF-targeted therapy, pretreated