Abstract
Tumor angiogenesis is a frequent event in the development and progression of non-small cell lung cancer (NSCLC) and has been identified as a promising therapeutic target. The vascular endothelial growth factor (VEGF) family and other angiogenic factors, including fibroblast growth factor and platelet-derived growth factor, promote the growth of newly formed vessels from preexisting vessels and change the tumor microenvironment. To date, two antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab, which target VEGF-A and its receptor VEGF receptor-2, respectively, have been approved for the treatment of locally advanced or metastatic NSCLC when added to first-line standard chemotherapy. Numerous oral multitargeting angiogenic small molecule tyrosine kinase inhibitors (TKIs) have been widely evaluated in advanced NSCLC, but only nintedanib in combination with platinum-based doublet chemotherapy has demonstrated a survival benefit in the second-line setting. Additionally, small-molecule TKIs remain the standard of care for patients with mutated EGFR, ALK or ROS1. Moreover, immune checkpoint inhibitors that target the programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) are changing the current strategy in the treatment of advanced NSCLC without driver gene mutations. The potential synergistic activity of antiangiogenic agents and TKIs or immunotherapy is an interesting topic of research. This review will summarize the novel antiangiogenic agents, antiangiogenic monotherapy, as well as potential combination therapeutic strategies for the clinical management of advanced NSCLC.
Highlights
Non-small cell lung cancer (NSCLC) accounts for nearly 85% of all lung cancer cases and is one of the frequently diagnosed malignancies
The suppression of tumor-induced angiogenesis has identified as an attractive treatment strategy for advanced NSCLC as well as other types of cancer
Bevacizumab has been approved as an antiangiogenic monoclonal antibody in the firstline treatment of advanced NSCLC, whereas secondline us with ramucirumab showed a survival benefit
Summary
Non-small cell lung cancer (NSCLC) accounts for nearly 85% of all lung cancer cases and is one of the frequently diagnosed malignancies. Bevacizumab is a humanized monoclonal antibody targeting VEGF, has been approved by the US Food and Drug Administration (FDA) as a standard regimen for advanced NSCLC in the first-line setting. In the phase III BEYOND trail enrolling 276 Chinese patients, PFS was significantly different between the combination group (gemcitabinecisplatin plus bevacizumab) and the group receiving chemotherapy alone (9.2 versus 6.5 months), and the ORR (54% versus 26%) and OS (24.3 versus 17.7 months) were significantly different between the two study arms [23]. The large SAiL study enrolling 2,212 patients confirmed that the combination therapy with bevacizumab and platinum-based chemotherapy has a manageable safety profile and offered a clinical survival benefit to patients with advanced NSCLC [24]. Retrospective data from the ECOG 4599 and the US Oncology network show that the continual use of bevacizumab until disease progression prolonged both PFS and OS [19, 29]
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