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Development of acquired resistance and rash: case report An approximately 54-year-old man developed acquired resistance during treatment with gefitinib, and rash during treatment with sintilimab and bevacizumab for advanced non-small-cell-lung-cancer (NSCLC). Subsequently, at the approximate age 55 years, he developed acquired resistance during treatment with sintilimab for advanced NSCLC [routes, durations of treatments to reactions onsets and outcomes not stated]. The man, who had history of smoking, presented to the hospital in March 2017 at the age of 53 years. After thorough investigation, he was diagnosed with stage IIIB advanced NSCLC with mediastinal lymph node metastasis. Between March 2017 and June 2017, he received pemetrexed and cisplatin and achieved a partial response (PR). Subsequently, he received radiation therapy and gimeracil/oteracil/tegafur [TS-1]. In October 2017, genotyping revealed EGFR exon 19 del mutation. In January 2018 progressive disease (PD) was noted. Thus, he started receiving targeted therapy with gefitinib 250 mg/day as the second-line therapy. In May 2018, he had PD with adrenal and liver metastasis; however, gefitinib therapy was continued until July 2018. Due to rapid resistance to targeted therapy at the age of ~54 years, a molecular testing of the adrenal biopsy sample was carried out in July 2018, which confirmed the presence of MET gene amplification and previous EGFR exon 19 del mutation. Immunohistochemistry showed PD-L1 expression of 15%. MET amplification was considered responsible for acquired resistance to gefitinib. Thus, the man was switched to bevacizumab 375mg combined with gefitinib 250 mg/day from July 2018 to October 2018. However, the disease continued to progress with increase in metastases. Owing to poor response to bevacizumab and gefitinib therapy and PD-L1 expression of 15%, from 11 November 2018, he was switched to sintilimab 200mg combined with bevacizumab 400mg, every 3 weeks for 4 times. Thereafter, he developed grade 3 rashes, which were attributed to bevacizumab and sintilimab. A PR was obtained after 4 weeks. After 6 months of progression free survival (PFS), disease progressed (at the age of ~55 years) without significant change in gene mutation profile. But, there was positive downregulation of PD-L1 (5%) after acquired resistance to sintilimab. Disease progression was considered secondary to acquired resistance to sintilimab. Subsequently, he was treated with sintilimab combined with docetaxel and catequentinib [anlotinib], yet the efficacy was limited. Eventually, he died in June 2019 due to disease progression. Zhang Y, et al. Unexpected favorable outcome to sintilimab plus bevacizumab in an EGFR-mutated non-small cell lung cancer patient: A case report. Thoracic Cancer 11: 803503604 2717-2722, No. 9, Sep 2020. Available from: URL: http://doi.org/10.1111/1759-7714.13569

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Reactions 26 Sep 2020 No. 1823