EGFR S768_D770dup

The present study indicates that furmonertinib may be a first-line treatment option for patients with non-small cell lung cancer harboring EGFR ex20ins mutation.

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.

These results suggest that specific mutations in EGFR exon 20 play a crucial role in SIP development, partially though hyper-activation of the PI3K/AKT and MAPK signaling pathways. This study presents the first in vitro model for SIP development, which could facilitate further investigations into SIP pathogenesis and preclinical studies for new therapeutic agents.

First line with Afatinib 40mg QD from 8/30/2018 to 2/13/2019...On May 19, 2022, a new line of treatment begins with Carboplatin plus Pemetrexed every 3 weeks for 4 cycles and then maintenance with Pemetrexed until present, with good tolerance and clinical benefit. This case report confirms the efficacy of second-line treatment with Amivantamab in EGFR ex20insertion NSCLC, even at the level of brain lesions. The treatment resulted in a prolonged survival with a good quality of life for the patient.

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.

Furthermore, rather than erlotinib (GlideScore: -5.564; MM/GBSA: -52.8044), gefitinib (-7.68; -47.317), and afatinib (-5.075; -44.64), furmonertinib (-11.085; -68.1575) and osimertinib (-10.031; -63.87) revealed favorable binding activity to EGFRex20ins, with furmonertinib being the most significant. Furmonertinib might have positive clinical efficacy to advanced NSCLC pts with EGFRex20ins on account of its favorable binding activity to EGFRex20ins. It may be the optimal choice for these pts in the future.

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.

Furthermore, rather than erlotinib (GlideScore: −5.564; MM/GBSA: −52.8044), gefitinib (−7.68; −47.317), and afatinib (−5.075; −44.64), furmonertinib (−11.085; −68.1575) and osimertinib (−10.031; −63.87) revealed favorable binding activity to EGFRex20ins, with furmonertinib being the most significant. Conclusions Furmonertinib has positive clinical efficacy to advanced NSCLC pts with EGFRex20ins probably based on its favorable binding activity to EGFRex20ins. Furmonertinib may be the optimal choice for these pts in the future.

Furthermore, rather than erlotinib (GlideScore: -5.564; MM/GBSA: -52.8044), gefitinib (-7.68; -47.317), and afatinib (-5.075; -44.64), furmonertinib (-11.085; -68.1575) and osimertinib (-10.031; -63.87) revealed favorable binding activity to EGFRex20ins, with furmonertinib being the most significant. Conclusions Furmonertinib has positive clinical efficacy to advanced NSCLC pts with EGFRex20ins probably based on its favorable binding activity to EGFRex20ins. Furmonertinib may be the optimal choice for these pts in the future.

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.

"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.

Although patients with EGFR exon 20 mutations accounted for only about 5% LUAD patients, and had worse response rates in general, certain subtypes had significantly different prognoses compared with other subtypes.

In general, patients with EGFR ex20ins shared a similar age and gender to patients with other EGFR mutations or without EGFR ex20ins. Overall, our results revealed the molecular and clinicopathologic features of EGFR ex20ins in Chinese LUAD patients, which will be helpful for drug development and in clinical trials targeting EGFR ex20ins.

We described the landscape of EGFR Ex20ins in Chinese NSCLC patients cohort. Based on the large sample size, the frequency of the Ex20ins mutation in Chinese NSCLC patients was 2.2%, and the types of EGFR Ex20ins mutation were highly heterogeneous.

Detection of EGFRex20ins is necessary to identify patients suitable for amivantamab and mobocertinib. Commonly used PCR assays may fail to detect EGFRex20ins in 50% of patients potentially suitable for approved targeted therapies. Identification of EGFRex20ins can be improved with NGS-based testing. Our data confirm that NGS is superior to PCR-based assays and is the preferred NSCLC genotyping technology.

Low PD-L1 expression and TMB were observed in NSCLC patients harboring EGFR ex20ins mutations. Further investigations are needed to confirm the therapeutic sensitivity of ICIs in this subgroup of EGFR mutations.

Specific targeted therapies are not available for patients with EGFR ex20ins+ NSCLC, regardless of insertion variant status; however, mobocertinib and amivantamab are currently in development. It is projected that commercially available PCR kits could have missed >40% of patients with NSCLC harboring ex20ins. Given the diverse profile of EGFR ex20ins variants, NGS-based genetic testing can substantially improve their identification in NSCLC.

Their therapies were changed to cetuximab combined with TKI of afatinib or osimertinib, and local treatment including local radiation, intraventricular pemetrexed administration, or with intrathoracic drain . Cetuximab-based systemic therapy combined with local treatment demonstrated preliminary clinical activity in the rare EGFR-mutant lung cancer with LM who have already undergone heavily previous therapy, warranting further investigation.

PFS and OS in this population remain poor. Understanding the role of co-occurring genomic alterations and their impact on outcomes may have therapeutic implications on clinical trial development.

Among 24 patients administered an EGFR-TKI, median PFS was longer in the non-EGFR amplification group than in the EGFR amplification group (110 vs. 31 days, P=0.030). There is a tendency that EGFR amplification might be a poor predictor in EGFR ex20ins-positive NSCLC patients treated with EGFR-TKIs.

Pemetrexed-based treatment could have better control of disease than non-pemetrexed-based chemotherapies in this population. Furthermore, more effective agents are expected for patients harboring EGFR ex20ins.

Common mutations and the number of concomitant mutations ≤1 correlate with a biomarker that predicts benefit from chemotherapy and confers excellent prognosis for advanced patients with advanced EGFR ex20ins NSCLC. Patients with common mutations and with only one concomitant mutation had the greatest PFS and patients with uncommon mutations, and with over one concomitant mutation had the worst prognosis.

Legal entity responsible for the study: Chunwei Xu. Funding: Has not received any funding.