There is renewed interest in MSI analysis because the MSI-H/dMMR phenotype has emerged as an actionable predictive biomarker for immune checkpoint blockade therapy in different cancer types. This review presents available evidence supporting the clinical relevance and predictive value of MSI/dMMR in cancers, including those treated with immune checkpoint inhibitors (ICIs), and outlines the diagnostic approaches developed to assess MSI/dMMR in clinical practice.
PD-L1 expression is a rational biomarker to predict response to PD-1/PD-L1 ICI therapy, and has been studied extensively in clinical trials. A recurring theme emerging from available clinical data is that high levels of tumor cell membrane PD-L1 expression correlate with better outcomes with PD-1/PD-L1 blockade.
More recently, immunologic therapy has emerged as an important treatment option for many types of cancers, based on demonstrations of unprecedented efficacy. This radical shift in treatment has come with the recognition of the essential role of the immune system in the surveillance and eradication of neoplastic cells, particularly modulation of the immune checkpoint protein cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and the programmed death-1 (PD-1) receptor and its ligand, PD-L1.
As the costs associated with cancer care continue to escalate, all key stakeholders—healthcare providers, private and government payers, and patients—strive to balance high-quality cancer care with cost efficiency. As insurance benefit designs continue to shift the cost burden of treatment, more patients with cancer and their families are both psychologically and financially invested in treatment decisions.
Lung cancer is the leading cause of death from cancer worldwide, estimated to be responsible for nearly 1 in 5 cancer deaths in 2012 (1.59 million deaths, 19.4% of total cancer deaths).1 In the United States, lung cancer is the second most frequently diagnosed cancer, with an estimated 224,390 new cases in 2016, representing the leading cause of cancer death in Americans.2,3