内容紹介
Summary
Background: In recent years, osimertinib has been increasingly used as a therapeutic drug for epidermal growth factor receptor(EGFR)mutation-positive lung cancer, with heart failure rarely reported as an adverse event. We report here a case of a significantly decreased ejection fraction and heart failure that were induced by osimertinib. We consider the case important and include a discussion of relevant previous reports. Case: The patient was a 73-year-old woman who had been on oral gefitinib as first-line treatment for EGFR mutation-positive(exon19 deletion)non-small cell lung cancer for approximately 1 year and 2 months. Thereafter, she tested positive for an EGFR resistance mutation(T790M); and accordingly, oral osimertinib was started at 80 mg/day as second-line treatment. After continuing this treatment for 6 months with no particular adverse events, she visited our hospital and was found to have dyspnea on exertion and increased pleural effusion. Based on these findings, cancer relapse was suspected, and the patient was hospitalized for detailed examinations. She was diagnosed with heart failure based on the elevated BNP level that was found in a blood test and CT and echocardiography findings, and her ejection fraction deteriorated to 19% from a pretreatment level of 59%. The conditions improved after diuretic and β-blocker treatment. Given the absence of any possible cause of heart failure or reduced ejection fraction in her past history of illness and medication, we concluded that these conditions were induced by osimertinib. Conclusion: While heart failure induced by EGFR-TKIs has been rarely reported, osimertinib may cause cardiomyopathy due to human epidermal growth factor receptor type 2(HER2)inhibitory activity.
要旨
背景: オシメルチニブはepidermal growth factor receptor(EGFR)遺伝子変異陽性肺癌の治療薬として近年多くの症例で使用されているが,有害事象として心不全の報告はまれである。今回,オシメルチニブによる著明な駆出率低下と心不全を認めた症例を経験し貴重であると考え,文献的考察を加え報告する。症例: 73歳,女性。EGFR遺伝子変異(exon 19欠失)陽性,非小細胞肺癌に対して一次治療としてゲフィチニブをおよそ1年2か月内服していた。その後耐性遺伝子(T790M)陽性となったため,入院の6か月前から二次治療としてオシメルチニブ80 mg/日を内服中であった。特に有害事象なく経過していたが,労作時呼吸困難および胸水の増加を認め,再発を疑い精査目的に入院となった。採血でのBNP上昇と胸部単純CTおよび心エコー所見から心不全の診断で利尿剤,β遮断薬を使用し改善を認めた。治療前は59%であった心駆出率が19%であり,心不全の原因となり得る既往歴や内服歴もないことからオシメルチニブによる駆出率低下,心不全と診断した。結論: EGFR-TKIsでの心不全の報告はまれではあるが,オシメルチニブにはHER2阻害作用があり,心筋障害を引き起こす可能性がある。
目次
Background: In recent years, osimertinib has been increasingly used as a therapeutic drug for epidermal growth factor receptor(EGFR)mutation-positive lung cancer, with heart failure rarely reported as an adverse event. We report here a case of a significantly decreased ejection fraction and heart failure that were induced by osimertinib. We consider the case important and include a discussion of relevant previous reports. Case: The patient was a 73-year-old woman who had been on oral gefitinib as first-line treatment for EGFR mutation-positive(exon19 deletion)non-small cell lung cancer for approximately 1 year and 2 months. Thereafter, she tested positive for an EGFR resistance mutation(T790M); and accordingly, oral osimertinib was started at 80 mg/day as second-line treatment. After continuing this treatment for 6 months with no particular adverse events, she visited our hospital and was found to have dyspnea on exertion and increased pleural effusion. Based on these findings, cancer relapse was suspected, and the patient was hospitalized for detailed examinations. She was diagnosed with heart failure based on the elevated BNP level that was found in a blood test and CT and echocardiography findings, and her ejection fraction deteriorated to 19% from a pretreatment level of 59%. The conditions improved after diuretic and β-blocker treatment. Given the absence of any possible cause of heart failure or reduced ejection fraction in her past history of illness and medication, we concluded that these conditions were induced by osimertinib. Conclusion: While heart failure induced by EGFR-TKIs has been rarely reported, osimertinib may cause cardiomyopathy due to human epidermal growth factor receptor type 2(HER2)inhibitory activity.
要旨
背景: オシメルチニブはepidermal growth factor receptor(EGFR)遺伝子変異陽性肺癌の治療薬として近年多くの症例で使用されているが,有害事象として心不全の報告はまれである。今回,オシメルチニブによる著明な駆出率低下と心不全を認めた症例を経験し貴重であると考え,文献的考察を加え報告する。症例: 73歳,女性。EGFR遺伝子変異(exon 19欠失)陽性,非小細胞肺癌に対して一次治療としてゲフィチニブをおよそ1年2か月内服していた。その後耐性遺伝子(T790M)陽性となったため,入院の6か月前から二次治療としてオシメルチニブ80 mg/日を内服中であった。特に有害事象なく経過していたが,労作時呼吸困難および胸水の増加を認め,再発を疑い精査目的に入院となった。採血でのBNP上昇と胸部単純CTおよび心エコー所見から心不全の診断で利尿剤,β遮断薬を使用し改善を認めた。治療前は59%であった心駆出率が19%であり,心不全の原因となり得る既往歴や内服歴もないことからオシメルチニブによる駆出率低下,心不全と診断した。結論: EGFR-TKIsでの心不全の報告はまれではあるが,オシメルチニブにはHER2阻害作用があり,心筋障害を引き起こす可能性がある。