TY - JOUR
T1 - Narrative review of the emerging role of molecular biomarkers in guiding the definitive management of unresectable non-small cell lung cancer
AU - Singhi, Eric K.
AU - Gay, Carl M.
N1 - Publisher Copyright:
© Translational Lung Cancer Research. All rights reserved.
PY - 2020/10
Y1 - 2020/10
N2 - 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.
AB - 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.
KW - Immunotherapy
KW - Targeted therapy
KW - Unresectable non-small cell lung cancer (unresectable NSCLC)
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U2 - 10.21037/tlcr-20-330
DO - 10.21037/tlcr-20-330
M3 - Review article
C2 - 33209625
AN - SCOPUS:85096112378
SN - 2218-6751
VL - 9
SP - 2051
EP - 2058
JO - Translational Lung Cancer Research
JF - Translational Lung Cancer Research
IS - 5
ER -