^
    6d
    EGFR-V834L combined with L858R mutation reduced afatinib sensitivity and associated to early recurrence in lung cancer. (PubMed, Transl Lung Cancer Res)
    The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib is widely used as a first-line treatment for EGFR-mutated non-small cell lung cancer (NSCLC). In three cases of EGFR-L858R+V834L, other co-mutations, including TP53, CTNNB1, and RB1, were detected either before or after afatinib resistance. These results suggested that V834L cooperates with other coexisting mutations to influence the therapeutic efficacy of EGFR-TKIs.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
    |
    TP53 mutation • EGFR mutation • EGFR L858R • EGFR T790M • EGFR V834L
    |
    Tagrisso (osimertinib) • Gilotrif (afatinib)
    1year
    Almonertinib plus olaparib treat epidermal growth factor receptor 21 exon V834L with ARID1A Q171 co-mutation in a patient with non-small cell lung cancer (APSR 2023)
    No abstract available
    Clinical • PARP Biomarker
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    ARID1A (AT-rich interaction domain 1A)
    |
    ARID1A mutation • EGFR V834L
    |
    Lynparza (olaparib) • Ameile (aumolertinib)
    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
    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)
    almost2years
    Overcoming CEP85L-ROS1, MKRN1-BRAF and MET amplification as rare, acquired resistance mutations to Osimertinib. (PubMed, Front Oncol)
    The first patient presented with EGFR L858R/L833V compound mutation with MET amplification alongside CEP85L-ROS1 fusion gene, the second with EGFR exon 19del and MKRN1-BRAF fusion, and the last EGFR L858R/V834L compound mutation with MET amplification. Each regimen utilized a tyrosine kinase inhibitor or monoclonal antibody in addition to osimertinib and allowed for a prompt and relatively durable treatment response.
    Preclinical • Journal
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    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CEP85L (Centrosomal Protein 85 Like)
    |
    EGFR mutation • BRAF mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification • ROS1 fusion • MET mutation • BRAF fusion • EGFR L833V • EGFR V834L
    |
    Tagrisso (osimertinib)
    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)
    3years
    Response with pemrbolizumab in a patient with EGFR mutated non-small cell lung cancer harbouring insertion mutations in V834L and L858R. (PubMed, J Oncol Pharm Pract)
    From our observation Pembrolizumab could be promising in patients with rare EGFR mutations who do not respond to EGFR directed therapy. Our report provides supporting data for the use of immunotherapies in patients with EGFR mutated NSCLC.
    Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR V834L • PD-L1 mutation
    |
    Keytruda (pembrolizumab)
    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)
    over4years
    Acquired resistance to osimertinib in patients with non-small-cell lung cancer: mechanisms and clinical outcomes. (PubMed, J Cancer Res Clin Oncol)
    The study revealed heterogeneous mechanisms of resistance to osimertinib in advanced NSCLC patients and their association with clinical outcomes. Patients who maintained T790M mutation or with EGFR-dependent resistance mechanism had longer clinical outcome benefits.
    Clinical • Clinical data • Retrospective data • Journal
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • PIK3CA mutation • MET amplification • EGFR T790M • EGFR amplification • EGFR C797S • PIK3CA amplification • EGFR mutation + KRAS mutation • EGFR G724S • BRAF mutation + MET amplification • EGFR T790M + KRAS mutation • EGFR mutation + EGFR T790M • EGFR C796S • EGFR C797S + EGFR C796S • EGFR E758D • EGFR G796S • EGFR V802I • EGFR V834L • EGFR mutation + EGFR T790M + EGFR C797S • KRAS mutation + EGFR amplification
    |
    Tagrisso (osimertinib)