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Published on: March 30, 2019
Therapeutic options targeting angiogenesis in nonsmall cell lung cancer
1Division of Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
Abstract:
There is a major unmet medical need for effective and well-tolerated treatment options for patients with advanced nonsmall cell lung cancer (NSCLC), in both first-line and relapsed/refractory settings. Experimental evidence has validated signalling pathways that regulate tumour angiogenesis, including the vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) pathways, as valid anti-cancer drug targets. However, to date, bevacizumab (an anti-VEGF monoclonal antibody) is the only antiangiogenic agent to be approved for the treatment of NSCLC. Many other agents, including antibodies, small-molecule tyrosine kinase inhibitors and vascular disrupting agents, have been assessed in phase III trials but have generally failed to demonstrate clinically meaningful benefits. This lack of success probably reflects the redundancy of proangiogenic pathways and the molecular and clinical heterogeneity of NSCLC. In this review we summarise recently completed and ongoing randomised clinical trials of emerging antiangiogenic agents in patients with NSCLC. We highlight recent promising data with agents that simultaneously inhibit multiple proangiogenic pathways, including the PDGF and FGF pathways, as well as the VEGF pathway. Finally, we discuss the outlook for antiangiogenic agents in NSCLC, emphasising the need for clinically validated prognostic and predictive biomarkers to identify patients most likely to respond to therapy.
Insights
New antiangiogenic agents targeting multiple pathways show promise for advanced nonsmall cell lung cancer (NSCLC). Identifying predictive biomarkers is crucial for patient selection and treatment success in NSCLC.
Area of Science:
- Oncology
- Cancer Research
- Translational Medicine
Background:
- Advanced nonsmall cell lung cancer (NSCLC) presents a significant unmet medical need for effective treatments.
- Targeting angiogenesis pathways like VEGF, PDGF, and FGF is a validated strategy, but only anti-VEGF agents are approved for NSCLC.
- Previous antiangiogenic agents have largely failed in Phase III trials due to pathway redundancy and tumor heterogeneity.
Purpose of the Study:
- To review recent and ongoing randomized clinical trials of novel antiangiogenic agents in NSCLC.
- To highlight promising data from agents targeting multiple proangiogenic pathways simultaneously.
- To discuss the future outlook for antiangiogenic therapies in NSCLC and the role of biomarkers.
Main Methods:
- Systematic review of completed and ongoing randomized clinical trials.
- Focus on emerging antiangiogenic agents, including those with multi-pathway inhibition.
- Analysis of clinical trial data and outcomes in patients with advanced NSCLC.
Main Results:
- Emerging antiangiogenic agents targeting multiple pathways (VEGF, PDGF, FGF) show promising preliminary data.
- Simultaneous inhibition of multiple proangiogenic pathways may overcome limitations of single-target agents.
- Clinical trial results are still emerging, with ongoing studies evaluating efficacy and safety.
Conclusions:
- Multi-targeted antiangiogenic agents represent a promising avenue for treating advanced NSCLC.
- Further research and clinical trials are needed to confirm the benefits of these novel agents.
- Development and validation of predictive biomarkers are essential to personalize antiangiogenic therapy in NSCLC.
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