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    Crizotinib in patients with tumors harboring ALK or ROS1 rearrangements in the NCI-MATCH trial.

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    Author
    Mansfield, A S
    Wei, Z
    Mehra, R
    Shaw, A T
    Lieu, C H
    Forde, P M
    Drilon, A E
    Mitchell, E P
    Wright, J J
    Takebe, N
    Sharon, E
    Hovelson, D
    Tomlins, S
    Zeng, J
    Poorman, K
    Malik, N
    Gray, R J
    Li, S
    McShane, L M
    Rubinstein, L V
    Patton, D
    Williams, P M
    Hamilton, S R
    Conley, B A
    Arteaga, C L
    Harris, L N
    O'Dwyer, P J
    Chen, A P
    Flaherty, K T
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    Date
    2022-03-01
    Journal
    NPJ Precision Oncology
    Publisher
    Springer Nature
    Type
    Article
    
    Metadata
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    See at
    https://doi.org/10.1038/s41698-022-00256-w
    Abstract
    The NCI-MATCH was designed to characterize the efficacy of targeted therapies in histology-agnostic driver mutation-positive malignancies. Sub-protocols F and G were developed to evaluate the role of crizotinib in rare tumors that harbored either ALK or ROS1 rearrangements. Patients with malignancies that progressed following at least one prior systemic therapy were accrued to the NCI-MATCH for molecular profiling, and those with actionable ALK or ROS1 rearrangements were offered participation in sub-protocols F or G, respectively. There were five patients who enrolled on Arm F (ALK) and four patients on Arm G (ROS1). Few grade 3 or 4 toxicities were noted, including liver test abnormalities, and acute kidney injury. For sub-protocol F (ALK), the response rate was 50% (90% CI 9.8–90.2%) with one complete response among the 4 eligible patients. The median PFS was 3.8 months, and median OS was 4.3 months. For sub-protocol G (ROS1) the response rate was 25% (90% CI 1.3–75.1%). The median PFS was 4.3 months, and median OS 6.2 months. Data from 3 commercial vendors showed that the prevalence of ALK and ROS1 rearrangements in histologies other than non-small cell lung cancer and lymphoma was rare (0.1% and 0.4% respectively). We observed responses to crizotinib which met the primary endpoint for ALK fusions, albeit in a small number of patients. Despite the limited accrual, some of the patients with these oncogenic fusions can respond to crizotinib which may have a therapeutic role in this setting. © 2022, The Author(s).
    Rights/Terms
    © 2022. The Author(s).
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/18218
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41698-022-00256-w
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