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Acute interstitial lung disease and development of resistance: case report A 67-year-old man developed acute interstitial-lung disease (ILD) during treatment with avitinib. Additionally, he developed resistance to erlotinib and osimertinib during treatment of metastatic lung adenocarcinoma [routes not stated; not all dosages and times to reactions onsets stated]. The man, who had EGFR 21 exon L858R-positive metastatic lung adenocarcinoma, exhibited disease progression after receiving erlotinib (progression-free survival [PFS] 8.0 months). An amplification refractory mutation system PCR in re-biopsied tumour tissue confirmed T790M-positive mutation. Erlotinib was withdrawn. Thereafter, the man was enrolled on a phase I trial (NCT02330367) in order to receive avitinib [AC0010]. One month later his adenocarcinoma had stabilised. However, on day 54 of avitinib therapy, he started experiencing dyspnoea, cough and fever. A lung CT scan showed diffuse ground-glass opacification in the lung. He was diagnosed with avitinib-induced acute ILD. Avitinib was discontinued. He was treated with methylprednisolone and unspecified empirical antibiotics. Thereafter, his ILD resolved. For the underlying adenocarcinoma, he was treated with pemetrexed. However, pemetrexed caused severe myelosuppression. Pemetrexed was then discontinued. Osimertinib 80 mg/day was subsequently administered under close monitoring, that resulted in partial remission. A PFS of 11 months was achieved. Following re-biopsy post progression on osimertinib, a pathological examination showed histological transformation from adenocarcinoma to large-cell neuroendocrine carcinoma. Meanwhile, the level of neuronspecfic enolase (NSE) in serum increased significantly, suggestive of neuroendocrine neoplasia (caused by progression of underlying adenocarcinoma). A next-generation sequencing based liquid biopsy revealed EGFR 21L858R mutation (the allelic frequency was 7.9%) without T790M mutation. No other gene variation with clear clinical significance was noted. Author comment: "Acquired T790M mutation was confirmed by re-biopsy after progression on erlotinib treatment." "Our case also shows that pathological transformation of large-cell neuroendocrine carcinoma is one of the resistance mechanisms of osimertinib." "The patient was diagnosed with [avitinib]-induced acute ILD." Wang H, et al. Successful treatment with osimertinib and its subsequent resistance mechanism in a patient with non-small-cell lung cancer harboring acquired EGFR T790M mutation after recovery from AC0010-induced interstitial lung disease. OncoTargets and Therapy 12: 5545-5549, Jul 2019. Available from: URL: http:// 803432501 doi.org/10.2147/OTT.S204689 - China

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Reactions 9 Nov 2019 No. 1778