Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most prevalent mutation in non-small cell lung cancer (NSCLC), following the 19del and L858R mutations. The unique nature of the EGFR ex20ins mutation poses challenges for the effectiveness of first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). As a result, chemotherapy remains the primary and more effective treatment approach. However, with advancements in time and technology, numerous experimental studies have revealed the potential of novel drugs and therapies to have stronger inhibitory effects on EGFR ex20ins mutations. In this comprehensive review, we provide an overview of the current treatment landscape, recent advancements, and the prospects for patients with advanced NSCLC characterized by EGFR ex20ins mutations.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11196869 | PMC |
http://dx.doi.org/10.3389/fonc.2024.1367204 | DOI Listing |
Expert Opin Drug Saf
February 2025
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Background: Amivantamab stands as the pioneering bispecific antibody that targets both EGFR and MET, utilized in the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR ex20ins mutations. Nevertheless, a thorough assessment of its safety characteristics in the real-world remains unknown.
Research Design And Methods: The adverse event (AE) reports were collected through a search of the FDA Adverse Event Reporting System (FAERS) database spanning from 2019 Q1 to 2024 Q1, and then disproportionality analysis was utilized.
Future Oncol
February 2025
Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
There remains a significant unmet need for effective and tolerable treatments for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor () exon 20 insertion (ex20ins) mutations in the first-line setting. First and later generation EGFR tyrosine kinase inhibitors (TKIs) have shown efficacy for common mutations; however, their effectiveness against ex20ins mutations is limited, and platinum-based chemotherapy remains part of the standard of care. Data suggest that combining chemotherapy with EGFR inhibitors offers promise for ex20ins-mutated NSCLC.
View Article and Find Full Text PDFJ Clin Oncol
January 2025
Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Chinese University of China, Shatin, Hong Kong Special Administrative Region, China.
Purpose: Mobocertinib is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that targets exon 20 insertion (ex20ins) mutations in non-small cell lung cancer (NSCLC). This open-label, phase III trial (EXCLAIM-2: ClinicalTrials.gov identifier: NCT04129502) compared mobocertinib versus platinum-based chemotherapy as first-line treatment of ex20ins+ advanced/metastatic NSCLC.
View Article and Find Full Text PDFJ Med Chem
February 2025
Pharmaron Beijing Co., Ltd., 6 Taihe Road, BDA, Beijing 100176, P. R. China.
Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.
View Article and Find Full Text PDFCancer Med
February 2025
Pulmonology and Thoracic Oncology Department, APHP Hôpital Tenon and Sorbonne Université, Paris, France.
Background: Real-world data regarding patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations receiving mobocertinib are limited. This study describes these patients' characteristics and outcomes.
Methods: A chart review was conducted across three countries (Canada, France, and Hong Kong), abstracting data from eligible patients (NCT05207423).
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!