EGFR A767_V769dup

In conclusion, MD simulations can effectively predict patient outcomes by connecting computational results with clinical data and advancing our understanding of EGFR mutations and their therapeutic responses.

EGFR-C797S in cis to all EGFR mutations evaluated generated dependent cells that were resistant to the covalent EGFR tyrosine kinase inhibitors mobocertinib, zipalertinib, furmonertinib, sunvozertinib, poziotinib, and osimertinib. This report highlights that poziotinib and mobocertinib are susceptible to on-target resistance mediated by EGFR-T790M or -C797S in the background of the most prevalent EGFR exon 20 insertion mutations. Furmonertinib, sunvozertinib, and to a less extent zipalertinib can overcome EGFR-T790M compound mutants, whereas EGFR-C797S leads to covalent inhibitor cross-resistance-robust data that support the limitations of mobocertinib and should further spawn the development of next-generation covalent and reversible EGFR exon 20 insertion mutation active inhibitors with favorable therapeutic windows that are less vulnerable to on-target resistance.

A new modality of treatment for NSCLC patients with EGFRx20ins has been established with the approval of mobocertinib and amivantamab. There are also numerous novel targeted treatments for NSCLC with EGFRex20ins in development, which are anticipated to improve this patient population's survival even further. This review provides a reference for the clinical management of these patients by summarizing the most recent epidemiological, and clinicopathological characteristics, diagnostic techniques, and therapeutic advances of EGFRex20ins in NSCLC.

This study investigated the distribution of EGFR E20ins in the Asian population, with p.A767_V769dup and p.S768_D770dup being the most frequently observed mutations. Since some studies have reported single EGFR E20ins sequences using different names, it is important to be cautious when describing EGFR E20ins. To ensure comprehensive coverage in real-world settings, each method used for the detection of EGFR E20ins must be annotated according to the HGVS nomenclature.

Furmonertinib has shown encouraging antitumor activity and CNS activity in patients with advanced NSCLC with EGFR ex20ins. Moreover, furmonertinib had a good safety profile and no dose-dependent toxicity.

Here we also explore amivantamab versus docetaxel (DOC), EGFR tyrosine kinase inhibitors (TKIs) or immuno-oncology (IO) in RW practice in Japan using a lung cancer genomic screening platform (LC-SCRUM-Asia) with more than 16,000 NSCLC pts from 2013. Conclusions Amivantamab-treated pts had better clinical benefits compared to DOC, TKIs and IO. Amivantamab should be considered a standard therapy after platinum-based chemotherapy for EGFR E20i aNSCLC pts.

The POSITION20 study showed modest antitumor activity in patients with EGFRex20 + NSCLC treated with 160 mg osimertinib, with a confirmed ORR of 28% and acceptable toxicity.

"Five of the 7 ex20ins were found in advanced stage patients, two of them received first line chemotherapy and two an EGFR TKI (afatinib or osimertinib), with short responses. Conclusion Implementation of NGS in routine clinical practice allows identifying rare ex20ins in EGFR, including new variants, which would be missed by other methodologies. New therapeutic approaches are needed for ex20ins p, which respond poorly to current treatments."

The ORR and median PFS of 2nd-4th line docetaxel with or without ramcirumab/bevacizumab were 29% and 6.1 months (95%CI, 5.1-8.5), respectively. The NSCLC patients with EGFR Ex20ins responded poorly to TKIs and had a worse prognosis compared to the NSCLC patients with EGFR common mutations. Development of a novel treatment strategy for EGFR Ex20ins is needed. The NSCLC patients with EGFR Ex20ins showed poor responses to PD-1/PD-L1 monotherapy and TKIs.

Further, 2nd generation TKI, afatinib significantly improved the TTF compared with 1st generation TKI. In this study, for the first time, we applied the structure-based classification approach to characterize the mutational landscape of EGFR-mutant patients in Chinese patients with NSCLC. Adopting this structure-function-based EGFR classification into clinical practice may improve the precision medicine for EGFR mutant NSCLC patients as well as benefit future drug development and clinical trial design.

The recently approved targeted drugs Amivantamab and Mobocertinib shift the treatment paradigm for NSCLC patients harboring EGFR exon 20 insertion mutations. There are also several new compounds targeting NSCLC EGFR exon 20 insertion mutations are in development. In this article, we provide a through overview on the treatment development in EGFR exon 20 insertion mutant NSCLC..