Abstract
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) greatly improve the survival and quality of life of non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, many patients exhibit de novo or primary/early resistance. In addition, patients who initially respond to EGFR-TKIs exhibit marked diversity in clinical outcomes. With the development of comprehensive genomic profiling, various mutations and concurrent (i.e., coexisting) genetic alterations have been discovered. Many studies have revealed that concurrent genetic alterations play an important role in the response and resistance of EGFR-mutant NSCLC to EGFR-TKIs. To optimize clinical outcomes, a better understanding of specific concurrent gene alterations and their impact on EGFR-TKI treatment efficacy is necessary. Further exploration of other biomarkers that can predict EGFR-TKI efficacy will help clinicians identify patients who may not respond to TKIs and allow them to choose appropriate treatment strategies. Here, we review the literature on specific gene alterations that coexist with EGFR mutations, including common alterations (intra-EGFR [on target] co-mutation, TP53, PIK3CA, and PTEN) and driver gene alterations (ALK, KRAS, ROS1, and MET). We also summarize data for other biomarkers (e.g., PD-L1 expression and BIM polymorphisms) associated with EGFR-TKI efficacy.
Highlights
Lung cancer is the most prevalent cancer type and is one of the leading causes of cancer-related death [1]
We summarize the data on other biomarkers (e.g., progressive disease (PD)-L1 expression and BIM polymorphisms) that appear to be associated with EGFR-TKI efficacy (Figure 1)
This report described the many studies on the efficacy of EGFRTKIs in patients with EGFR-mutant non-small cell lung cancer (NSCLC) with coexisting intraEGFR or other gene mutations and molecular markers that may predict EGFR-TKI efficacy
Summary
Lung cancer is the most prevalent cancer type and is one of the leading causes of cancer-related death [1]. Many studies have demonstrated that concurrent genetic alterations potentially impair TKI efficacy and partly explain the heterogeneous patient outcomes [8,9,10]. Sato et al [11] found that PFS for EGFR-TKIs in EGFR-mutant lung adenocarcinoma was associated with the number of concurrent genomic alterations. The types of genomic alterations coexisting with EGFR mutations may be associated with EGFR-TKI efficacy. Recent studies have demonstrated that at a small percentage [16,17,18], additional driver alterations coexist with EGFR mutations in TKI therapy-naïve NSCLC and may impact EGFR-TKI efficacy and partly explain the intrinsic resistance in some patients [19].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
