Checkpoint Inhibitors in Non-small Cell Lung Cancer: Potentials and Challenges

Immune checkpoint inhibitors are one of the most recent breakthroughs in cancer immunotherapy, which have changed the treatment paradigm in many types of solid tumors, including melanoma, gastrointestinal cancers, renal cancer, and non-small cell lung cancer. Among all, plenty of the commercially available checkpoint inhibitors are approved as first- or second-line therapies for non-small cell lung cancer patients, including nivolumab, pembrolizumab, atezolizumab, durvalumab, and, most recently, cemiplimab. Moreover, a number of recently developed checkpoint inhibitors are currently being investigated in active trials, and thus, improving the efficiency of these agents has been a dynamic area of research. To this end, a number of biomarkers have been developed to aid clinicians choose the “right” patients before initiating the treatment, as well as monitor their response through the course of therapy. Further, to minimize the challenges associated with the use of checkpoint inhibitors in these patients, including their associated adverse events and resistance to therapy, a thorough understanding of the tumor biology and the complex interactions within the tumor milieu is crucial. In this chapter, an overview of both currently approved and under-investigation checkpoint inhibitors for non-small cell lung cancer is presented, along with a survey on their biomarkers of response. Furthermore, we take a look at the challenges associated with checkpoint inhibitor treatment in these patients and review the most current strategies to overcome these challenges. Since the existing literature on these emerging issues is extensive, only the most important findings are highlighted in each section to give the audience a comprehensive outlook of the topic, and the enthusiastic reader is therefore referred to the mentioned references for further details.