The Potential of Combined Immunotherapy and Antiangiogenesis for the Synergistic Treatment of Advanced NSCLC

Abstract

Over the past few years, there have been considerable advances in the treatments available to patients with metastatic or locally advanced NSCLC, particularly those who have progressed during first-line treatment. Some of the treatment options available to patients are discussed here, with a focus on checkpoint inhibitor immunotherapies (nivolumab and pembrolizumab) and antiangiogenic agents (bevacizumab, ramucirumab, and nintedanib). It is hypothesized that combining immunotherapy with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments. In this review, we explore the theory and potential of this novel treatment option for patients with advanced NSCLC. We discuss the growing body of evidence that proangiogenic factors can modulate the immune response (both by reducing T-cell infiltration into the tumor microenvironment and through systemic effects on immune-regulatory cell function), and we examine the preclinical evidence for combining these treatments. Potential challenges are also considered, and we review the preliminary evidence of clinical efficacy and safety with this novel combination in a variety of solid tumor types.

Improved efficacy of ramucirumab plus docetaxel after nivolumab failure in previously treated non‐small cell lung cancer patients

“…VEGF plays a crucial role in mediating the immunosuppressive microenvironment. In particular, VEGFR2 inhibition is reported to significantly increase cluster of differentiation (CD)4‐positive and CD8‐positive T cell infiltration and reduce the number of Tregs and MDSCs within tumor tissues in mice . A recent experimental study showed that simultaneous inhibition of PD‐1 and VEGFR2 significantly suppressed tumor growth compared to monotherapy .…”

Activity of Pembrolizumab in Recurrent Cervical Cancer

“…Moreover, the combination of bevacizumab and checkpoint inhibitors or other immunotherapies also seems to have a synergistic effect and is currently investigated for other solid tumor such as ovarian cancer. 19 When interpreting the findings of our report, some limitations typical for retrospective studies need to be kept in mind. Previously reported studies have used RECIST 1.1 criteria.…”

Historical Evolution of Second-Line Therapy in Non-Small Cell Lung Cancer

“…Emerging evidence that pro-angiogenic factors have immunosuppressive activity has suggested that agents targeting angiogenesis may be potentially synergistic with immunotherapy (67–69). Data from literature indicate that VEGF influences lymphocyte trafficking, stimulates T regulatory cells and myeloid-derived suppressor cells, and inhibits T-cell development, thus favoring tumor immune escape (70–72).…”