Immune Checkpoint Inhibitors in Thoracic Malignancies: Review of the Existing Evidence by an IASLC Expert Panel and Recommendations

Abstract

In the past 10 years, a deeper understanding of the immune landscape of cancers, including immune evasion processes, has allowed the development of a new class of agents. The reactivation of host antitumor immune response offers the potential for long-term survival benefit in a portion of patients with thoracic malignancies. The advent of programmed cell death protein 1/programmed death ligand-1 immune checkpoint inhibitors (ICIs), both as single agents and in combination with chemotherapy, and more recently, the combination of ICI, anti-programmed cell death protein 1, and anticytotoxic T-lymphocyte antigen 4 antibody, have led to breakthrough therapeutic advances for patients with advanced NSCLC, and to a lesser extent, patients with SCLC. Encouraging activity has recently emerged in pretreated patients with thymic carcinoma (TC). Conversely, in malignant pleural mesothelioma, pivotal positive signs of activity have not been fully confirmed in randomized trials. The additive effects of chemoradiation and immunotherapy suggested intriguing potential for therapeutic synergy with combination strategies. This has led to the introduction of ICI consolidation therapy in stage III NSCLC, creating a platform for future therapeutic developments in earlier-stage disease. Despite the definitive clinical benefit observed with ICI, primary and acquired resistance represent well-known biological phenomena, which may affect the therapeutic efficacy of these agents. The development of innovative strategies to overcome ICI resistance, standardization of new patterns of ICI progression, identification of predictive biomarkers of response, optimal treatment duration, and characterization of ICI efficacy in special populations, represent crucial issues to be adequately addressed, with the aim of improving the therapeutic benefit of ICI in patients with thoracic malignancies. In this article, an international panel of experts in the field of thoracic malignancies discussed these topics, evaluating currently available scientific evidence, with the final aim of providing clinical recommendations, which may guide oncologists in their current practice and elucidate future treatment strategies and research priorities.

Keywords: Biomarkers; Consensus; Immune checkpoint inhibitors; Microbiome; Non–small cell lung cancer; Small cell lung cancer.