Immune Checkpoint Blockade in Oncogene-Driven Non-Small-Cell Lung Cancer

Patients with oncogene-driven lung cancer have limited therapeutic options after progressing on their targeted tyrosine kinase inhibitor (TKI) therapy. Given the growing role of immune checkpoint inhibitor (ICI) therapy in the treatment of lung cancer, oncogene-driven cancer has warranted further evaluation regarding ICI therapy. However, initial ICI studies have suggested that ICI monotherapy is not only lacking in efficacy, but that it may be less tolerable in oncogene-driven non-small-cell lung cancer (NSCLC). We performed a detailed review of the literature using Pubmed, and present the current and impactful findings here. Studies evaluating the use of concurrent ICI therapy and TKI therapy have also suggested increased toxicity and lack of increased activity in these patients. Larger studies have suggested that the sequence of ICI therapy and TKI, such as utilizing ICI therapy after TKI as opposed to before TKI, may play a role in reducing toxicity (hepatotoxicity, pneumonitis); however, these studies are limited in number. Novel methods of patient selection, including low tumor mutational burden, inflamed phenotyping, and  high CD8 + tumor infiltrating lymphocytes, may aid in determining ideal patients to give ICI therapy. Novel therapeutic combinations including the addition of anti-VEGF (vascular endothelial growth factor) therapy or radiotherapy show promising findings for these patients. Given the growing unmet need for therapeutic options in patients with oncogene-driven NSCLC who have failed TKI therapy, further research is warranted.