Crizotinib
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Development of crizotinib resistance: case report. A woman in her 30s [exact age not stated] exhibited resistance to crizotinib, indicated for ROS1 fusion-positive lung cancer. The woman presented at the age of 32 years, with decreased exercise tolerance and persistent dry cough. CT scan of the chest showed bilateral nodules and extensive multifocal areas of mass-like consolidation. Biopsy of tumour revealed adenocarcinoma with mixed lepidic and micropapillary patterns. The tumour cells were positive for thyroid transcription factor-1 (TTF-1) and cytokeratin 7 (CK7). Subsequently, she received 4 cycles of chemotherapy including pemetrexed, carboplatin and bevacizumab, which eventually resulted in radiological and clinical improvement. Fluorescence in situ hybridisation revealed a ROS1 rearrangement. Therefore, she was enrolled in a phase 1 clinical trial in order to receive crizotinib. She received crizotinib 250mg twice daily [route not stated], and exhibited 30.1% of tumour reduction, which was considered as best response. After 43 months, examinations revealed continued response with isolated progression of the left lower lobe lung nodule. A repeat biopsy of this nodule demonstrated adenocarcinoma. Targeted next-generation sequencing confirmed a G2032R (c.6094G>A) mutation in the domain of ROS1 kinase (acquired resistance). Two single-nucleotide variants N263D (c.787A>G) and W146 (c.437G>A) were detected in TP53. She continued crizotinib, and was treated with stereotactic body radiation therapy for growing nodules. Further examinations demonstrated an adjacent left lower lobe nodule, which was treated with microwave ablation. After 57 months of crizotinib initiation, repeat evaluations revealed two new hepatic metastases. Crizotinib was withdrawn. The woman received taletrectinib [DS-6051b] and an unspecified investigational ROS1 inhibitor. However, her primary progression persisted with newly identified enlarged hepatic metastasis. Subsequently, she received chemotherapy of short courses including pemetrexed, carboplatin, bevacizumab, cabozantinib and lorlatinib. However, no tumour response was noted. Treatment was discontinued, and after 69 months of the initial diagnosis, she died [immediate cause of death not stated]. Lin JJ, et al. Small cell transformation of ROS1 fusion-positive lung cancer resistant to ROS1 inhibition. npj Precision Oncology 4: 21, No. 1, 2020. Available from: URL: 803499909 http://doi.org/10.1038/s41698-020-0127-9
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Reactions 5 Sep 2020 No. 1820
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