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    Association details:
    Biomarker:ROS1 D2033N
    Cancer:Non Small Cell Lung Cancer
    Drug:Xalkori (crizotinib) (ALK inhibitor)
    Direction:Sensitive
    Evidence:
    Evidence Level:
    Sensitive: C3 – Early Trials
    New
    Source:
    JCO Precis Oncol
    Title:

    Patterns of Metastatic Spread and Mechanisms of Resistance to Crizotinib in ROS1-Positive Non–Small-Cell Lung Cancer

    Excerpt:
    Additionally, we identified 16 patients who underwent a total of 17 repeat biopsies following progression on crizotinib. ROS1 resistance mutations were identified in 53% of specimens, including 9/14 (64%) non-brain metastasis specimens. ROS1 mutations included: G2032R (41%), D2033N (6%), and S1986F (6%).
    DOI:
    10.1200/PO.17.00063
    Evidence Level:
    Sensitive: C3 – Early Trials
    New
    Source:
    J Thorac Oncol
    Title:

    P1.14-50 A Phase 2 Trial of Cabozantinib in ROS1-Rearranged Lung Adenocarcinoma

    Excerpt:
    Progression on crizotinib can be mediated by the acquisition of ROS1 kinase domain mutations (e.g. ROS1G2032R or ROS1D2033N). Cabozantinib is a highly potent ROS1 tyrosine kinase inhibitor that has superior activity over lorlatinib against these mutations. We evaluated the activity of cabozantinib in patients with ROS1-rearranged lung cancers on a phase 2 trial.
    DOI:
    https://doi.org/10.1016/j.jtho.2019.08.1201
    Evidence Level:
    Sensitive: C3 – Early Trials
    New
    Source:
    JCO Precis Oncol
    Title:

    Patterns of Metastatic Spread and Mechanisms of Resistance to Crizotinib in ROS1-Positive Non–Small-Cell Lung Cancer

    Excerpt:
    CONTRADICTING EVIDENCE: Additionally, we identified 16 patients who underwent a total of 17 repeat biopsies following progression on crizotinib. ROS1 resistance mutations were identified in 53% of specimens, including 9/14 (64%) non-brain metastasis specimens. ROS1 mutations included: G2032R (41%), D2033N (6%), and S1986F (6%).
    DOI:
    10.1200/PO.17.00063
    Evidence Level:
    Sensitive: C4 – Case Studies
    New
    Source:
    Clin Cancer Res
    Title:

    A novel crizotinib-resistant solvent-front mutation responsive to cabozantinib therapy in a patient with ROS1-rearranged lung cancer

    Excerpt:
    CONTRADICTING EVIDENCE: A 50 year-old female never smoker with metastatic lung adenocarcinoma...While these data strongly suggest that ROS1D2033N is a novel acquired crizotinib-resistant mutation…
    DOI:
    10.1158/1078-0432.CCR-15-2013
    Evidence Level:
    Sensitive: C4 – Case Studies
    New
    Source:
    Clin Cancer Res
    Title:

    A novel crizotinib-resistant solvent-front mutation responsive to cabozantinib therapy in a patient with ROS1-rearranged lung cancer

    Excerpt:
    A 50 year-old female never smoker with metastatic lung adenocarcinoma...While these data strongly suggest that ROS1D2033N is a novel acquired crizotinib-resistant mutation…
    DOI:
    10.1158/1078-0432.CCR-15-2013