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Abstract
<p class="first" id="d12218676e77">Lung cancer remains the leading cause of cancer
deaths in the United States. In the
past decade, significant advances have been made in the science of non-small cell
lung cancer (NSCLC). Screening has been introduced with the goal of early detection.
The National Lung Screening Trial found a lung cancer mortality benefit of 20% and
a 6.7% decrease in all-cause mortality with the use of low-dose chest computed tomography
in high-risk individuals. The treatment of lung cancer has also evolved with the introduction
of several lines of tyrosine kinase inhibitors in patients with EGFR, ALK, ROS1, and
NTRK mutations. Similarly, immune checkpoint inhibitors (ICIs) have dramatically changed
the landscape of NSCLC treatment. Furthermore, the results of new trials continue
to help us understand the role of these novel agents and which patients are more likely
to benefit; ICIs are now part of the first-line NSCLC treatment armamentarium as monotherapy,
combined with chemotherapy, or after definite chemoradiotherapy in patients with stage
III unresectable NSCLC. Expression of programmed cell death protein-ligand 1 in malignant
cells has been studied as a potential biomarker for response to ICIs. However, important
drawbacks exist that limit its discriminatory potential. Identification of accurate
predictive biomarkers beyond programmed cell death protein-ligand 1 expression remains
essential to select the most appropriate candidates for ICI therapy. Many questions
remain unanswered regarding the proper sequence and combinations of these new agents;
however, the field is moving rapidly, and the overall direction is optimistic.
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