Developmental antiangiogenic agents for the treatment of Non-Small Cell Lung Cancer (NSCLC)

Abstract

Standard therapy for advanced or metastatic non-small cell lung cancer (NSCLC) has primarily consisted of traditional cytotoxic chemotherapy, although use of targeted therapies has been approved in specific settings. Antiangiogenic agents represent a promising therapeutic strategy for treatment of advanced NSCLC. Bevacizumab is currently approved when given in combination with first-line platinum-based therapy in selected patients with nonsquamous NSCLC. Bevacizumab may also provide benefit in other clinical settings, as a part of a combination or maintenance strategy. Other antiangiogenic agents under development, including multi-targeted kinase inhibitors (MTKIs) and antibody-based agents, have exhibited mixed results in the NSCLC population. Published efficacy and safety data from clinical trials for antiangiogenic agents are reviewed, with an emphasis on novel agents and novel settings for established agents. Identification of biomarkers associated with improved efficacy may help select patients likely to receive the most benefit from these agents and may improve outcomes through development of personalized therapeutic strategies.

The Role of Tumor Inflammatory Microenvironment in Lung Cancer

“…Traditional surgery, radiotherapy, and chemotherapy are still the only treatment options for most advanced NSCLC patients, but these treatments are unsatisfactory (Choi et al, 2010). Consequently, more and more studies have begun to investigate lung cancer from the perspective of the TME, especially inflammation; actively explore targets related to anti-angiogenesis, immune regulation, and EMT in the microenvironment; and develop more therapeutic targets (Blumenschein, 2012). For example, Logsdon et al found that in the presence of carcinogenic Ras, inflammatory stimulation initiates a positive feedback loop involving NF-κB, which further amplifies the activity of Ras to the pathological level (Figure 6).…”

Challenges in Developing a Validated Biomarker for Angiogenesis Inhibitors: The Motesanib Experience

“…The important role of angiogenesis in tumor development, growth, and metastasis is well established [1] . Angiogenesis inhibitors, including the anti−vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab; the recombinant anti-VEGF fusion protein aflibercept; and the receptor tyrosine kinase inhibitors sorafenib, sunitinib, axitinib, vandetanib, and pazopanib, have been shown to improve outcomes for patients with certain cancer types, either as monotherapy or combined with chemotherapy [2] – [4] . However, only a fraction of treated patients typically derive clinical benefit.…”

The Management of Brain Metastases in Non-Small Cell Lung Cancer

“…Supportive therapy, surgery, and RT remain the mainstays of management for these patients. Additional areas of active research include techniques to preserve neurocognitive functions with radiotherapy (20, 52), improving the detection and clinical utility of circulating tumor cells (53), and novel systemic approaches including immunotherapy alone (54, 55) or in combination with radiotherapy (56), anti-metabolic agents (57), anti-angiogenesis drugs (58), and novel targeted therapies for a growing list of oncogenic mutations (59). Ultimately, the optimal management strategy will employ a multi-disciplinary approach accounting for individual characteristics of both patient and tumor.…”