Narrative review of the emerging role of molecular biomarkers in guiding the definitive management of unresectable non-small cell lung cancer.

The addition of PD-L1 targeting consolidation therapy to previously standard of care concurrent chemoradiation for locally advanced, unresectable non-small cell lung cancer resulted in dramatic improvements in clinical outcomes. However, in contrast to patients with metastatic disease, the application of immunotherapies is not currently guided by molecular characteristics of patient tumors. Furthermore, despite increasing awareness of predictive and/or prognostic genomic alterations in patients with locally advanced disease, the utility of targeted therapies, such as those aimed at alterations in EGFR or ALK , remains unclear in this subset of patients. As a result, patients with unresectable, locally advanced non-small cell lung cancer are treated uniformly according to histology, regardless of other molecular features despite the potential for treatment-associated risks without a clear benefit. Here, we first discuss the advantages of utilizing molecular biomarkers to guide treatment of non-small cell lung cancer based on treatment outcomes in the metastatic setting. Next, we review preclinical and retrospective clinical data that supports potential further personalization of these treatment strategies in earlier stages of disease. Finally, we discuss some of the ongoing clinical trials attempting to address these hypotheses prospectively.
Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-330). The series “New era of treatment for unresectable locally advanced non-small cell lung cancer” was commissioned by the editorial office without any funding or sponsorship. CG reports grants from AstraZeneca. The other author has no other conflicts of interest to declare.
(2020 Translational Lung Cancer Research. All rights reserved.)