^
    over4years
    Treatment with Next-Generation ALK Inhibitors Fuels Plasma ALK Mutation Diversity. (PubMed, Clin Cancer Res)
    ALK resistance mutations increase with each successive generation of ALK TKI and may be underestimated by tumor genotyping. Sequential treatment with increasingly potent ALK TKIs may promote acquisition of ALK resistance mutations leading to treatment-refractory compound ALK mutations.
    Journal
    |
    ALK (Anaplastic lymphoma kinase)
    |
    ALK positive • ALK mutation • ALK G1202R • ALK L1196M • ALK L1196M + ALK G1202R
    |
    Guardant360® CDx
    |
    Alecensa (alectinib) • Lorbrena (lorlatinib)
    over4years
    Diverse resistance mechanisms to the third-generation ALK inhibitor lorlatinib in ALK-rearranged lung cancer. (PubMed, Clin Cancer Res)
    This study shows that mechanisms of resistance to lorlatinib are diverse and complex, requiring new therapeutic strategies to tailor treatment upon disease progression.
    Journal
    |
    ALK (Anaplastic lymphoma kinase)
    |
    ALK rearrangement • ALK mutation • ALK G1202R • ALK C1156Y • ALK G1269A • ALK L1196M • ALK C1156Y + ALK G1202R • ALK L1196M + ALK G1202R
    |
    Lorbrena (lorlatinib)
    over4years
    Acquired multiple mutations ALK I1171N, L1196M and G1202R mediate lorlatinib resistance in EML4-ALK-rearranged malignant pleural mesothelioma: a case report. (PubMed, Ther Adv Respir Dis)
    EML4-ALK rearranged malignant pleural mesothelioma (MPM) is rare and its responses to anaplastic lymphoma kinase (ALK) inhibitors, including alectinib and lorlatinib, remain unexplored. Moreover, our case also revealed acquired mechanisms of lorlatinib resistance mediated by multiple mutations ALK I1171N, L1196M, and G1202R, contributing an incremental step to our understanding of the complexity of acquired resistance mechanisms in sequential ALK inhibitor therapy. The reviews of this paper are available via the supplemental material section.
    Clinical • Journal
    |
    ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4)
    |
    ALK rearrangement • ALK G1202R • ALK I1171N • EML4-ALK L1196M • ALK I1171 • ALK L1196M • EML4-ALK G1202R • ALK L1196M + ALK G1202R
    |
    Alecensa (alectinib) • Lorbrena (lorlatinib)
    over4years
    [VIRTUAL] Longitudinal monitoring by next generation sequencing of plasma cell-free DNA in ALK-rearranged non-small cell lung cancer (NSCLC) patients treated with ALK tyrosine kinase inhibitors. (ASCO 2020)
    " From April 2015 to July 2019, 92 patients enrolled; 81 (88.0%) received ALK TKI as first-line (crizotinib, n = 59; alectinib, n = 22), 10 (10.9%) received TKI as second-line (alectinib, n = 6; crizotinib, n = 2; ceritinib, n = 1; brigatinib, n = 1), and 1 (1.1%) was treated in third-line (lorlatinib). NGS of cell-free plasma DNA is useful not only for the detection of ALK fusions and resistance mutations but also for assessing prognosis and monitoring the dynamic changes of genomic alterations in ALK+ NSCLC treated with ALK TKI. Research Funding: Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No.NRF-2017M3A9G5060259)Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Kor"
    Clinical
    |
    ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • EML4 (EMAP Like 4) • TPM3 (Tropomyosin 3)
    |
    ALK rearrangement • EML4-ALK fusion • ALK fusion • ALK mutation • ALK G1202R • ALK G1269A • EML4-ALK L1196M • ALK L1196M • EML4-ALK G1202R • EML4-ALK G1269A • ALK L1196M + ALK G1202R
    |
    Guardant360® CDx
    |
    Xalkori (crizotinib) • Alecensa (alectinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib)
    over4years
    [VIRTUAL] Brigatinib in Japanese ALK positive NSCLC patients previously treated with ALK tyrosine kinase inhibitors: J-ALTA. (ASCO 2020)
    Brigatinib showed clinically meaningful efficacy in Japanese patients refractory to prior alectinib (first line or post crizotinib), regardless of prior chemotherapy. The safety profile of brigatinib was consistent with prior studies and no new safety findings were identified. Research Funding: Takeda Pharmaceutical Company Ltd
    Clinical
    |
    ALK (Anaplastic lymphoma kinase)
    |
    ALK positive • ALK rearrangement • ALK G1202R • ALK I1171N • ALK I1171 • ALK L1196M • ALK V1180L • ALK L1196M + ALK G1202R
    |
    Xalkori (crizotinib) • Alecensa (alectinib) • Alunbrig (brigatinib)