News - EGFR L747_P753delinsS

5ms

Analysis of Uncommon EGFR Exon 19 Alterations Identified by Liquid Biopsy in Advanced Non-Small Cell Lung Cancer (NSCLC) (IASLC-WCLC 2024)

Conclusions : To our knowledge, this is the largest liquid biopsy analysis comparing common/uncommon ex19dels in NSCLC and shows similar genomic findings across groups. Further work should be done to explore additional genomic and non-genomic factors to aid in patient selection for EGFR TKIs for uncommon findings.

5 months ago

Liquid biopsy • Metastases • Biopsy

EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR2 (Fibroblast growth factor receptor 2)

EGFR exon 19 deletion • MET amplification • EGFR T790M • FGFR2 fusion • EGFR C797S • EGFR G724S • EGFR L747_A750delinsP • BRAF amplification • EGFR L747_P753delinsS

Guardant360® CDx

over1year

Clinical outcomes of patients with advanced NSCLC with different EGFR exon 19 deletion subtypes treated with first-line tyrosine kinase inhibitors. (ASCO 2023)

In advanced NSCLC patients with EGFR Ex19del, the efficacy of first-line TKIs therapy was affected by the presence of pleural metastasis, Ex19del subtypes and different generation of TKIs.

over 1 year ago

Clinical • Clinical data • Metastases

EGFR (Epidermal growth factor receptor)

EGFR exon 19 deletion • EGFR T790M • EGFR E746_S752delinsV • EGFR E746 • EGFR L747_P753delinsS

almost2years

A case and the landscape of coexisting EGFR mutation in non-small cell lung cancer (NSCLC) with microsatellite instability (MSI) high and tumor mutation burden (TMB) high traits. (IASLC-TTLC 2023)

For 462 samples with EGFR wildtype and MSS trait, median TMB was 5.18 (Q1: 2.59, Q3: 8.64) and 99 (21.4%) samples had TMB-H trait (>10 mut/Mbp). CONCLUSION In summary, we report, for the first time, a rare case of EGFR-mutated NSCLC with MSI-H and TMB-H traits currently responding well to osimertinib.

almost 2 years ago

Clinical • Microsatellite instability • Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • MLH1 (MutL homolog 1) • TSC2 (TSC complex subunit 2) • NKX2-1 (NK2 Homeobox 1) • INPP4B (Inositol polyphosphate-4-phosphatase type II B) • ERCC5 (ERCC Excision Repair 5 Endonuclease 2)

TP53 mutation • EGFR mutation • TMB-H • MSI-H/dMMR • HER-2 overexpression • EGFR L858R • EGFR exon 19 deletion • PTEN mutation • EGFR wild-type • TMB-L • MLH1 mutation • TSC2 mutation • EGFR L747_P753delinsS

VENTANA PD-L1 (SP263) Assay

Tagrisso (osimertinib)

2years

Comparison of next-generation sequencing and cobas EGFR mutation test v2 in detecting EGFR mutations. (PubMed, Thorac Cancer)

The success rate of ODxTT is slightly inferior to that of cobas EGFR. ODxTT shared a high concordance rate and k-coefficient with cobas EGFR in detecting EGFR mutations, but discordant results between the two tests were observed in a few cases, mainly due to the difference of detectable EGFR variants.

2 years ago

Journal • Next-generation sequencing

EGFR (Epidermal growth factor receptor)

EGFR mutation • EGFR exon 19 deletion • EGFR L861R • EGFR E746 • EGFR L747_P753delinsS

cobas® EGFR Mutation Test v2 • Oncomine™ Dx Target Test

almost3years

A multicenter-retrospective study of non-small-cell lung carcinoma harboring uncommon epidermal growth factor receptor (EGFR) mutations: different subtypes of EGFR exon 19 deletion-insertions exhibit the clinical characteristics and prognosis of non-small cell lung carcinoma. (PubMed, Transl Lung Cancer Res)

The EGFR exon 19 deletion-insertion mutations exhibited limited sensitivity to 3rd generation TKI. Moreover, in light of therapeutic effect for the subtype, L747_T751delinsP achieved longer PFS.

almost 3 years ago

Retrospective data • Journal

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RB1 (RB Transcriptional Corepressor 1) • NAPSA (Napsin A Aspartic Peptidase)

TP53 mutation • EGFR mutation • PIK3CA mutation • EGFR exon 19 deletion • EGFR E746_S752delinsV • EGFR L747_A750delinsP • EGFR E746 • EGFR L747_P753delinsS • EGFR L747_T751delinsP

3years

Patients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M. (PubMed, BMC Cancer)

This retrospective cohort study furnish the evidence that therapeutic responses and survival of untreated NSCLC population with EGFR 19delins mutation are equal to those with common EGFR 19del mutation after administration of EGFR TKIs therapy.

3 years ago

Clinical • Journal

EGFR (Epidermal growth factor receptor)

EGFR mutation • EGFR exon 19 deletion • EGFR T790M • EGFR E746_S752delinsV • EGFR L747_A750delinsP • EGFR E746 • EGFR L747_P753delinsS

over3years

[VIRTUAL] Molecular characteristics of EGFR exon 19 deletion subtypes in NSCLC patients. (ASCO 2021)

EGFR exon 19 starting at codon 729 to 761, our data showed the deletions occur throughout almost the entire exon 19 amino acid . As our integrated data results, EGFR exon 19 has many different deletions and insertion subtypes could be defined as 79 subtypes . Among those subtypes,70 were complex with an accompanying insertion .

over 3 years ago

Clinical

EGFR (Epidermal growth factor receptor)

EGFR mutation • EGFR exon 19 deletion • EGFR E746_S752delinsV • EGFR E746 • EGFR L747_P753delinsS

4years

[VIRTUAL] Comprehensive Investigation of Uncommon EGFR Mutations in 14,429 Chinese Lung Cancer Patients (IASLC-WCLC 2020)

Conclusion More and more uncommon EGFR mutations are identified owing to the development of NGS. This is the largest NGS-based cohort of Chinese lung cancers for investigating uncommon EGFR mutations, and 5.48% patients that with EGFR-TKI-sensitive uncommon mutations alone were found, which should be informative for the clinical therapies.

4 years ago

Clinical

EGFR (Epidermal growth factor receptor)

EGFR mutation • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR G719S • EGFR exon 18 mutation • EGFR G719C • EGFR A750P • EGFR E746 • EGFR L747_P753delinsS