Biomarker Testing in Lung Cancer—What Does It Mean?

Abstract

The study by Leapman and colleagues 1 presents the results of an analysis of the Flatiron Health Database concentrating on the use of programmed cell death ligand 1 (PD-L1) testing and immune checkpoint inhibitors (ICIs) in patients with previously untreated, metastatic non-small cell lung cancer (NSCLC). The good news is that there has been rapid uptake of testing and use of ICIs in the appropriate population. Furthermore, as studies have been reported that expanded the indication for treatment with ICIs, practitioners quickly adopted these new approaches, frequently ahead of regulatory authorities. The bad news is that enthusiasm for these agents also led to overuse, in that a substantial proportion of patients whose PD-L1 status was less than 1 or who were untested received single-agent pembrolizumab, despite evidence that the drug was less effective than standard chemotherapy in this population.Management of patients with a diagnosis of metastatic NSCLC has changed dramatically in recent years. 2 Molecular testing using a comprehensive next-generation sequencing platform is now a standard part of our treatment algorithm, with at least 7 actionable variants known (ie, with an available US Food and Drug Administration-approved agent) and others likely to emerge in the near future. 3,4 As noted, PD-L1 testing has also become standard, based on the results of a number of studies showing an association between level of PD-L1 expression and clinical efficacy of ICIs. [5][6][7] Given this wealth of developments and increasing complexity of treatment algorithms, it is imperative that biomarker testing be correctly interpreted and used. Data from the current report 1 indicate that PD-L1 testing has had rapid uptake; however, other studies have found less use of molecular markers, such as epidermal growth factor receptor and anaplastic lymphoma kinase, among others. 4 This could be because of the ease of obtaining an immunohistochemistry-based assay, such as those for PD-L1 expression, vs the more tissue-and time-consuming process of DNA