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

Christian Manegold, Anne-Marie C. Dingemans, Jhanelle E. Gray, Kazuhiko Nakagawa, Marianne Nicolson, Solange Peters, Martin Reck, Yi-Long Wu, Odd Terje Brustugun, Lucio Crinò, Enriqueta Felip, Dean Fennell, Pilar Garrido, Rudolf M. Huber, Aurélien Marabelle, Marcin Moniuszko, Françoise Mornex, Silvia Novello, Mauro Papotti, Maurice Pérol, Egbert F. Smit, Kostas Syrigos, Jan P. van Meerbeeck, Nico van Zandwijk, James Chih-Hsin Yang, Caicun Zhou, Everett Vokes

Over the past few years, there have been considerable advances in the treatments available to patients with metastatic or locally advanced non-small cell lung cancer (NSCLC), particularly those who have progressed on or 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 hypothesised 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 pro-angiogenic factors can modulate the immune response (both by reducing T-cell infiltration into the tumour microenvironment, and through systemic effects on immune-regulatory cell function) and 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 tumour types.