Rapidly progressive arthropathy identified on imaging of patients treated with Crizotinib for ALK-rearranged/ROS1-positive non small cell lung cancer: A retrospective single-center study

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OBJECTIVES: Progressive arthropathy was anecdotally described in patients exposed to crizotinib, a receptor tyrosine kinases inhibitor (TKI) used to treat anaplastic lymphoma kinase (ALK) or ROS Proto-Oncogene 1 (ROS1) positive non-small cell lung cancer (NSCLC). We aimed to evaluate the incidence of this adverse effect. METHODS: We retrospectively evaluated imaging studies of all patients in our institution receiving TKI for ALK-rearranged or ROS1-positive NSCLC (crizotinib, alectinib, lorlatinib, brigatinib). RESULTS: Between February 2012 and August 2023, out of a total number of 71 subjects (51% male, 36-88 years old) who received TKI's for ALK-rearranged/ ROS1 positive NSCLC, 34/71 (47%) were exposed at least once to crizotinib treatment, while the other 37/71 (53%) patients received other TKI's. Significantly higher incidence (p = 0.02) of irreversible, progressive arthropathy in one or more joints was detected in 18% (6/34, 95% CI: 0.1-0.26) of crizotinib-treated patients, up to 6 years after treatment initiation. Imaging findings included synovial proliferation and progressive arthropathy in hip and shoulder joints, and vertebral endplate destruction. CONCLUSION: We found progressive arthropathy, mostly painless, in one or more joints or intervertebral spaces of patients receiving crizotinib for NSCLC.

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