Advances in Immunotherapy and Implications for Current Practice in Non–Small-Cell Lung Cancer

Conor E. Steuer, MD; Suresh S. Ramalingam, MD


J Oncol Pract. 2021;17(11):662-668. 

In This Article

Abstract and Introduction


Treatment options for patients with non–small-cell lung cancer (NSCLC) have improved dramatically in recent years. For decades, harnessing a person's own immune system to fight cancer has been a major area of research in oncology. Recently, these efforts have proven successful with the development of immune checkpoint inhibitors; these agents have now become part of the routine care of NSCLC. Presently, five programmed cell death-1 and programmed cell death-1 ligand 1 inhibitors and one anti–cytotoxic T-cell lymphocyte-4 inhibitor are US Food and Drug Administration–approved in the treatment of NSCLC. These drugs have made a dramatic difference in the lives of patients with NSCLC, although durable benefits are limited to a subset of patients. In this review, we highlight the trials that led to our current treatment practices, discuss areas of active research, and address common clinical issues that have risen as immune therapy has become a mainstay of treatment in NSCLC.


The interplay between cancer and the immune system has been the focus of extensive research over the past few decades, with the goal of harnessing the body's natural defenses to combat cancer development and progression. The importance of immune regulation and cancer's ability to evade this surveillance is now known to be a crucial component of tumorigenesis.[1] Only relatively recently has immunotherapy (IO) become a mainstay in treatment of non–small-cell lung cancer (NSCLC), beginning with the first US Food and Drug Administration (FDA) approvals of checkpoint inhibitors in the year 2015. Discovery and subsequent blockade of the immune regulatory programmed cell death-1 (PD-1) and programmed cell death-1 ligand 1 (PD-L1) pathway transformed the prognosis for patients diagnosed with NSCLC. In fact, recently it was shown that lung cancer mortality is decreasing overall and treatments such as PD-1 inhibitors have played a major role in this decline.[2] Currently, five PD-1 and PD-L1 inhibitors and one anti–cytotoxic T-cell lymphocyte-4 inhibitor are FDA-approved in the treatment of NSCLC. In this review, we will discuss the clinical trials that led to these approvals and use in practice, areas of active research, and finally our approach to common clinical scenarios with IO.