Antiangiogenic agents and chemotherapy in advanced non-small cell lung cancer: a clinical perspective

Abstract

Antiangiogenic agents represent a major advance in the management of patients with advanced non-small-cell lung cancer receiving chemotherapy. While bevacizumab has been available for first-line treatment, other drugs, such as nintedanib, recently demontrated significant activity in the second-line setting. This review covers most recent results with antiangiogenic treatments, focusing on data relevant for routine clinical practice; recent results potentially leading to new agents approval are discussed. While biomarkers are still awaited to better-select patients for these approaches, the development of antiangiogenic agents represent a model for implementation in thoracic oncology, while highlighting the promise of a better outcome for patients with advanced lung cancer.

Keywords::

• bevacizumab
• lung cancer
• neoangiogenesis
• nintedanib
• VEGF

Financial & competing interests disclosure

N Girard has occasionally served as a consultant for Hoffman-LaRoche, AstraZeneca, and Eli-Lilly, and has received travel grants to attend international oncology meetings from Hoffman-LaRoche, Eli-Lilly, and Boehringer-Ingelheim. This review was conducted independently from any industry support. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Antiangiogenic agents represent a major advance in the management of patients with advanced lung cancer receiving chemotherapy.

• • Bevacizumab is a recombinant humanized monoclonal IgG1 antibody neutralizing VEGF that is approved for first-line treatment, in combination with platin-based induction chemotherapy and subsequently as maintenance treatment.

• • The risk of severe bleeding initially a matter of concern with the use of bevacizumab is now accurately managed through better selection of eligible patients.

• • The optimal platin-based doublet to be combined with bevacizumab remains to be determined; eligibility of patients to cisplatin vs carboplatin is a major point to consider.

• • Nintedanib is a tyrosine kinase inhibitor targeting VEGFR-1, -2, -3, PDGFR-α and -β, and FGFR-1, -2, -3.

• • Nintedanib has been developed in combination with second-line chemotherapy for advanced lung cancer.

• • Recently one randomized trial reported that nintedanib, when combined with docetaxel, significantly prolonged the survival of a subset of patients with lung adenocarcinoma tumors.

• • Biomarkers are yet to be identified to predict the efficacy of antiangiogenic agents in lung cancer.