ABSTRACT
Personalized patient-precise medicine is being gradually incorporated into clinical practice for the treatment of non-small-cell lung cancer (NSCLC). The EGFR pathway has been explored as a druggable target with monoclonal antibodies such as cetuximab or necitumumab. Necitumumab is a humanized IgG1 anti-EGFR. In the Phase III SQUIRE trial, necitumumab used as first-line therapy in combination with cisplatin and gemcitabine showed a reduction in risk-of-death and a better disease control rate in advanced squamous NSCLC. Thus, necitumumab is now a new first-line treatment option in squamous NSCLC. However, further biomarker research is needed to improve patient selection. Moreover, necitumumab associated with other immunotherapy and targeted agents is currently an important area of research that may yield better outcomes for NSCLC patients.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal, Humanized , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/pharmacology , Cisplatin/therapeutic use , Clinical Trials as Topic , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Humans , GemcitabineABSTRACT
INTRODUCTION: Nintedanib (BIBF 1200) is an oral tyrosine kinase inhibitor that targets the vascular endothelial growth factor (VEGFR), platelet-derived growth factor (PDGFR) and fibroblast growth factor (FGFR) receptors. It is approved in Europe in combination with docetaxel for patients with advanced lung adenocarcinoma who have progressed to first-line chemotherapy. However, its role in the treatment of metastatic colorectal cancer (mCRC) is uncertain. Recent results from the LUME-Colon 1 pivotal phase III trial showed only a marginal increase in progression free survival over placebo in refractory mCRC patients, with a toxicity profile similar to other antiangiogenic agents, and no benefit in overall survival. Areas covered: The aim of this review is to summarize the pharmacology, efficacy and safety profile of nintedanib in the context of mCRC, and to provide some perspective regarding the role of this drug in clinical practice. Expert commentary: Nintedanib provides limited clinical benefit in refractory CRC and its use in this clinical setting is not warranted. Efforts shall continue to pursue the identification of predictive biomarkers that allow the selection of subpopulations with a greater likelihood to benefit from this therapeutic approach, in order to improve the benefit-risk and cost-benefit ratios of this and other antiangiogenic agents.
