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    BIOMARKER:

    EGFR exon 19 insertion

    i
    Other names: EGFR, ERBB, ERBB1, Epidermal growth factor receptor
    Entrez ID:
    1956
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    3ms
    Pulmonary adenocarcinoma: EGFR exon 19 insertion – report of 3 cases (ECP 2024)
    The sequenced adenocarcinomas presented predominant acinar pattern as well as solid, papillary/micropapillary and lepidic patterns, respectively, without relevance for the mutational status. Multiple parallel sequencing (MPS) allows accumulation of tumoural mutational knowledge overtaking concise standardized mutational equipment. Considering effective lab costs, clinical decisions for therapeutic available options and MPS is now the more advisable method.
    Clinical
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR exon 19 insertion
    |
    Oncomine Precision Assay
    5ms
    Efficacy of EGFR-Tyrosine Kinase Inhibitors in Patients with NSCLC Harboring EGFR Exon 19 Insertions: A Report from the LC-SCRUM-Asia (IASLC-WCLC 2024)
    We also studied preclinical Ba/F3 models expressing EGFR -K745_E746insIPVAIK (Ba/F3-IPVAIK) and EGFR -delE746_A750 (Ba/F3-Del19) to investigate the sensitivity to 1st-generation (gen) (gefitinib and erlotinib), 2nd-gen (afatinib, dacomitinib, and poziotinib), 3rd-gen (osimertinib), and EGFR exon 20 insertion active TKIs (mobocertinib, sunvozertinib, and zipalertinib). The preclinical therapeutic window of Ba/F3-IPVAIK and Ba/F3-Del19 for all the 2nd generation TKIs were similarly favorable, whereas Ba/F3-IPVAIK had much unfavorable therapeutic windows to other EGFR-TKIs compared to Ba/F3-Del19. Conclusions : Our clinical and preclinical findings indicate 2nd-gen EGFR-TKIs are more effective than 1st and 3rd-gen EGFR-TKIs in patients with EGFR exon 19 insertions.
    Clinical
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR (Fibroblast Growth Factor Receptor) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    TP53 mutation • EGFR mutation • PIK3CA mutation • EGFR amplification • EGFR exon 20 insertion • EGFR expression • FGFR mutation • EGFR exon 20 mutation • EGFR K745_E746insIPVAIK • EGFR mutation + PIK3CA mutation • EGFR exon 19 insertion • EGFR E746
    |
    Oncomine Precision Assay
    |
    Tagrisso (osimertinib) • erlotinib • Gilotrif (afatinib) • gefitinib • Vizimpro (dacomitinib) • Pozenveo (poziotinib) • Exkivity (mobocertinib) • sunvozertinib (DZD9008) • zipalertinib (CLN-081)
    over1year
    NCI-2019-05913: Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer (clinicaltrials.gov)
    P1, N=22, Active, not recruiting, Collin Blakely | Recruiting --> Active, not recruiting | N=38 --> 22 | Trial completion date: Feb 2025 --> May 2025 | Trial primary completion date: Feb 2025 --> May 2025
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    EGFR (Epidermal growth factor receptor) • TPX2 (TPX2 Microtubule Nucleation Factor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR E709K • EGFR exon 19 insertion • EGFR H835L • EGFR L833V • EGFR V834L
    |
    Tagrisso (osimertinib) • alisertib (MLN8237)
    over1year
    Molecular Characteristics and Response to TKIs in NSCLC Patients with EGFR Exon 19 Insertions (IASLC-WCLC 2023)
    Results from in vitro experiments suggested that the EGFR I740_K745dup mutation might be more sensitive to afatinib. Our comprehensive analysis of EGFR 19ins in lung cancer patients revealed genomic characteristics and clinical response that are distinct from 19del/delins. Our findings help better inform clinical action and might facilitate the development of more precise therapeutic options for patients with these uncommon driver mutations.
    Clinical • Tumor mutational burden
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden)
    |
    EGFR mutation • PIK3CA mutation • EGFR exon 19 deletion • EGFR T790M • EGFR exon 19 insertion • EGFR E746
    |
    Gilotrif (afatinib)
    over1year
    EGFR exon 19 insertion EGFR-K745_E746insIPVAIK and others with rare XPVAIK amino-acid insertions: Preclinical and clinical characterization of the favorable therapeutic window to all classes of approved EGFR kinase inhibitors. (PubMed, Lung Cancer)
    This is the largest preclinical/clinical report to highlight that EGFR-K745_E746insIPVAIK and other mutations with exon 19 XPVAIK amino-acid insertions are rare but sensitive to clinically available 1st, 2nd, and 3rd generation as well as EGFR exon 20 active TKIs; in a pattern that mostly resembles the outcomes of models with EGFR-L861Q and EGFR-A763_Y764insFQEA mutations. These data may help with the off-label selection of EGFR TKIs and clinical expectations of outcomes when targeted therapy is deployed for these EGFR mutated lung cancers.
    Preclinical • Journal
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR L861Q • EGFR A763_Y764insFQEA • EGFR exon 20 mutation • EGFR G719S • EGFR exon 19 deletion + EGFR L861Q • EGFR exon 19 insertion • EGFR E746
    |
    Tagrisso (osimertinib) • erlotinib • Gilotrif (afatinib) • gefitinib • Conmana (icotinib) • Exkivity (mobocertinib)
    over1year
    NCI-2019-05913: Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer (clinicaltrials.gov)
    P1, N=38, Recruiting, Collin Blakely | Trial completion date: Dec 2023 --> Feb 2025 | Trial primary completion date: Dec 2023 --> Feb 2025
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    EGFR (Epidermal growth factor receptor) • TPX2 (TPX2 Microtubule Nucleation Factor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR E709K • EGFR exon 19 insertion • EGFR H835L • EGFR L833V • EGFR V834L
    |
    Tagrisso (osimertinib) • alisertib (MLN8237)
    almost3years
    NCI-2019-05913: Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer (clinicaltrials.gov)
    P1, N=38, Recruiting, Collin Blakely | Trial completion date: May 2023 --> Dec 2023 | Trial primary completion date: May 2023 --> Dec 2023
    Trial completion date • Trial primary completion date • Combination therapy
    |
    EGFR (Epidermal growth factor receptor) • TPX2 (TPX2 Microtubule Nucleation Factor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR E709K • EGFR exon 19 insertion • EGFR H835L • EGFR L833V • EGFR V834L
    |
    Tagrisso (osimertinib) • alisertib (MLN8237)
    over3years
    Uncommon single and compound EGFR mutations: clinical outcomes of a heterogeneous subgroup of NSCLC. (PubMed, Curr Probl Cancer)
    For mutations in exon 18 (not in codon 719) and exon 20 insertions, chemotherapy seems the most effective available option. The addition of immunotherapy to chemotherapy could change this approach in the next future.
    Clinical • Clinical data • Journal • IO biomarker
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR exon 18 mutation • EGFR exon 19 insertion
    |
    Tagrisso (osimertinib) • Gilotrif (afatinib) • gefitinib
    over3years
    NCI-2019-05913: Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer (clinicaltrials.gov)
    P1, N=38, Recruiting, Collin Blakely | Trial completion date: Sep 2024 --> May 2023 | Trial primary completion date: Sep 2022 --> May 2023
    Trial completion date • Trial primary completion date • Combination therapy
    |
    EGFR (Epidermal growth factor receptor) • TPX2 (TPX2 Microtubule Nucleation Factor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR E709K • EGFR exon 19 insertion • EGFR V834L
    |
    Tagrisso (osimertinib) • alisertib (MLN8237)
    almost4years
    Stereotactic Body Radiation Therapy (SBRT) in Newly Diagnosed Advanced Staged Lung Adenocarcinoma (Sindas) (clinicaltrials.gov)
    P3, N=200, Terminated, Sichuan Provincial People's Hospital | Trial completion date: Dec 2023 --> Aug 2020 | Recruiting --> Terminated | Trial primary completion date: Dec 2021 --> Aug 2020; After interim analysis, IRB recommend termination.
    Trial completion date • Trial termination • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR S768I • EGFR G719A • EGFR exon 19 insertion
    |
    erlotinib • gefitinib
    4years
    Stereotactic Body Radiation Therapy (SBRT) in Newly Diagnosed Advanced Staged Lung Adenocarcinoma (Sindas) (clinicaltrials.gov)
    P3, N=200, Recruiting, Sichuan Provincial People's Hospital | Trial completion date: Dec 2021 --> Dec 2023 | Trial primary completion date: Dec 2020 --> Dec 2021
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR S768I • EGFR G719A • EGFR exon 19 insertion
    |
    erlotinib • gefitinib
    4years
    Stereotactic Body Radiation Therapy (SBRT) in Newly Diagnosed Advanced Staged Lung Adenocarcinoma (Sindas) (clinicaltrials.gov)
    P3, N=200, Recruiting, Sichuan Provincial People's Hospital | Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Dec 2019 --> Dec 2020
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR S768I • EGFR G719A • EGFR exon 19 insertion
    |
    erlotinib • gefitinib
    almost6years
    Local Therapies for Oligometastatic Non-Small Cell Lung Cancer Harboring Sensitizing EGFR Mutations (clinicaltrials.gov)
    P=N/A, N=4, Completed, Memorial Sloan Kettering Cancer Center | Recruiting --> Completed | Trial primary completion date: May 2018 --> Dec 2017
    Clinical • Trial completion • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR S768I • EGFR G719A • EGFR exon 19 insertion
    |
    erlotinib
    over7years
    Erlotinib Treatment Beyond Progression in EGFR Mutant NSCLC (clinicaltrials.gov)
    P2; N=18; Completed; Sponsor: Finnish Lung Cancer Group; Recruiting --> Completed; N=80 --> 18
    Enrollment change • Trial completion • Clinical
    |
    EGFR L858R • EGFR L861Q • EGFR G719A • EGFR G719S • EGFR G719C • EGFR exon 19 insertion
    |
    cisplatin • erlotinib • carboplatin • paclitaxel • docetaxel • pemetrexed