AI Article Synopsis

  • * A case study of a 34-year-old patient shows that after initial crizotinib treatment, the disease progressed, requiring a switch to chemotherapy and later multiple treatments, including whole-brain radiotherapy.
  • * The results suggest that switching to the drug entrectinib may help alleviate symptoms related to central nervous system metastases in ROS1-fusion-positive lung cancer patients who do not respond to crizotinib.

Article Abstract

Introduction: C-ros oncogene 1 (ROS1) translocation is an oncogenic driver-mutation identified in 1-2% of non-small-cell lung cancer (NSCLC) cases. Although crizotinib, a tyrosine kinase inhibitor (TKI) against ALK/ROS1, is known to be effective against ROS1-fusion-positive NSCLC, such cases sometimes progress with brain metastases. The most frequently reported crizotinib-resistance mutation is ROS1 G2032R, and some studies have found that even newly developed ROS1 TKIs, such as entrectinib and lorlatinib, show a decreased efficacy against it. The optimal therapies for ROS1-fusion-positive NSCLC and how such cases can be sequenced have not yet been established.

Case Presentation: We herein report a patient with ROS1-fusion-positive NSCLC diagnosed at 34 years old. Crizotinib was started at the diagnosis and switched after 25 months to cisplatin/pemetrexed/bevacizumab once the disease progressed with multiple brain metastases that were resistant to stereotactic radiation therapy. The cytotoxic chemotherapy stabilized the patient's condition for 17 months until he developed leptomeningeal metastasis (LM). He underwent lumboperitoneal shunting and whole-brain radiotherapy, followed by crizotinib re-administration. Despite crizotinib treatment, his neurological symptoms, such as double vision, headache, weakness in the legs, and walking difficulties, progressed. Eventually, subsequent entrectinib treatment was initiated, which resolved all of the symptoms mentioned above. Regrettably, liquid next-generation sequencing had failed to detect the resistance mechanism due to minimal ctDNA in this case.

Conclusion: These findings imply that sequential entrectinib administration may be effective in patients with disease progression limited to central nervous system metastases during crizotinib administration.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10715754PMC
http://dx.doi.org/10.1159/000534549DOI Listing

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