Biomarker-Targeted Therapies in Non–Small Cell Lung Cancer: Current Status and Perspectives

Abstract

Non-small-cell lung cancer (NSCLC) is one of the most common malignancies and the leading causes of cancer-related death worldwide. Despite many therapeutic advances in the past decade, NSCLC remains an incurable disease for the majority of patients. Molecular targeted therapies and immunotherapies have significantly improved the prognosis of NSCLC. However, the vast majority of advanced NSCLC develop resistance to current therapies and eventually progress. In this review, we discuss current and potential therapies for NSCLC, focusing on targeted therapies and immunotherapies. We highlight the future role of metabolic therapies and combination therapies in NSCLC.

Racial and Ethnic Inequities at the Practice and Physician Levels in Timely Next-Generation Sequencing for Patients With Advanced Non–Small-Cell Lung Cancer Treated in the US Community Setting

“…Cancer care for patients with advanced non–small-cell lung cancer (aNSCLC) has transformed into a personalized, precision approach with several targeted therapies approved by the US Food and Drug Administration (FDA) that require actionable oncogenic drivers identified through biomarker testing. 1 Standard-of-care biomarker testing has evolved from single-gene hotspot testing to comprehensive genomic profiling performed via next-generation sequencing (NGS). 2 While incorporation of biomarker testing into routine clinical practice has increased over time, 3,4 rates of comprehensive and timely NGS testing continue to lag behind guideline and society recommendations.…”

Clinical Outcomes of PD-1/PD-L1 Inhibitors Among Patients With Advanced or Metastatic Non–Small Cell Lung Cancer With BRAF, ERBB2/HER2, MET, or RET Alterations: A Systematic Literature Review

“…[2][3][4] Promisingly, however, the therapeutic landscape for patients with advanced or metastatic NSCLC is rapidly evolving due to advances in molecular testing and the development of new therapies targeting specific molecular alterations. 2,[5][6][7][8] Recent studies show that a large proportion (28%-44%) of patients with NSCLC have tumors expressing biomarkers that are targetable by first-line (1L) or subsequent therapies approved for advanced or metastatic NSCLC. [9][10][11] These biomarkers include genetic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 (ROS1), B-Raf proto-oncogene (BRAF), Erbb2 receptor tyrosine-protein kinase 2 (ERBB2)/human epidermal growth factor receptor 2 (HER2), Kirsten rat sarcoma virus (KRAS), MET proto-oncogene (MET), neurotrophic tyrosine receptor kinase (NTRK), and rearranged during transfection (RET).…”

“…3,4 Thus, by considering tumor molecular profiles together with other patient characteristics, such as tumor histology, clinicians are increasingly able to select treatment regimens that are most likely to improve the clinical outcomes of individual patients with advanced or metastatic NSCLC. [2][3][4][5][6][7][8] In addition to molecularly targeted therapies, immunotherapies including programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have also dramatically changed the way that NSCLC is treated and have led to survival benefits among patients with advanced or metastatic NSCLC with any PD-L1 expression level. 12 Today, PD-1/PD-L1 inhibitors are predominately used in the 1L setting for patients with advanced or metastatic NSCLC whose tumors do not harbor EGFR, ALK, or ROS1 alterations.…”

“…Most (80%–90%) patients with lung cancer have non–small cell lung cancer (NSCLC), of whom ~70% are diagnosed in the advanced or metastatic stage 2–4 . Promisingly, however, the therapeutic landscape for patients with advanced or metastatic NSCLC is rapidly evolving due to advances in molecular testing and the development of new therapies targeting specific molecular alterations 2,5–8 . Recent studies show that a large proportion (28%–44%) of patients with NSCLC have tumors expressing biomarkers that are targetable by first-line (1L) or subsequent therapies approved for advanced or metastatic NSCLC 9–11 .…”

“…These biomarkers include genetic alterations in epidermal growth factor receptor ( EGFR ), anaplastic lymphoma kinase ( ALK ), ROS proto-oncogene 1 ( ROS1 ), B-Raf proto-oncogene ( BRAF ), Erbb2 receptor tyrosine-protein kinase 2 ( ERBB2) /human epidermal growth factor receptor 2 ( HER2 ), Kirsten rat sarcoma virus ( KRAS ), MET proto-oncogene ( MET ), neurotrophic tyrosine receptor kinase ( NTRK ), and rearranged during transfection ( RET ) 3,4 . Thus, by considering tumor molecular profiles together with other patient characteristics, such as tumor histology, clinicians are increasingly able to select treatment regimens that are most likely to improve the clinical outcomes of individual patients with advanced or metastatic NSCLC 2–8 …”