内容紹介
Summary
Tropomyosin-related kinase(TRK)fusion proteins are oncogenic drivers in multiple tumors in adults and children. Larotrectinib, an orally administered selective TRK inhibitor approved in the US, exhibits inhibitory activity against tumors harboring TRK fusions and is well tolerated. Here, we report the case of an 8-year-old female child with recurrence of an NTRK fusion low-grade sarcoma treated with larotrectinib monotherapy. The patient previously underwent resection of low-grade sarcoma in the right brachialis at 6 years of age, but local recurrence occurred after 16 months. As re-operation likely required amputation, larotrectinib was commenced at a dose of 100 mg BID. Complete radiographic remission was achieved after 3 months. There were no adverse events attributed to larotrectinib treatment. After dosing for 6 months, we performed local resection, confirming pathological complete remission. The drug was stopped, and the patient showed no evidence of relapse at 4 months after resection. In this case, larotrectinib was obtained using Single Patient Expanded Access under the FDA. In this paper, we also discuss the issues faced while accessing unapproved drugs in the precision medicine era in Japan.
要旨 症例は8歳,女児。6歳時に右上腕に発生した軟部肉腫の腫瘍切除術が行われたが,16か月後に局所再発を起こした。初発時の腫瘍検体を用いたRNA seqデータより LMNA-NTRK1 融合遺伝子が検出されていたことから,larotrectinibの治験への参加を検討した。しかし当時小児を対象とした国内での治験が行われておらず,院内倫理委員会での承認を経て,米国食品医薬品局(FDA)のSingle Patient Expanded Access制度に申請し,larotrectinibによる治療を開始した。投薬開始3か月後には画像上の完全寛解(complete remission: CR)が得られ,さらに6か月治療を継続した後,試験切除を行い組織学的CR(pCR)を確認した。今回この症例の治療経過を報告するとともに,今後日本でも普及していくゲノム医療により同定されたまれなドライバー変異に対する治療法へのアクセス方法の課題について考察を加えて報告する。
目次
Tropomyosin-related kinase(TRK)fusion proteins are oncogenic drivers in multiple tumors in adults and children. Larotrectinib, an orally administered selective TRK inhibitor approved in the US, exhibits inhibitory activity against tumors harboring TRK fusions and is well tolerated. Here, we report the case of an 8-year-old female child with recurrence of an NTRK fusion low-grade sarcoma treated with larotrectinib monotherapy. The patient previously underwent resection of low-grade sarcoma in the right brachialis at 6 years of age, but local recurrence occurred after 16 months. As re-operation likely required amputation, larotrectinib was commenced at a dose of 100 mg BID. Complete radiographic remission was achieved after 3 months. There were no adverse events attributed to larotrectinib treatment. After dosing for 6 months, we performed local resection, confirming pathological complete remission. The drug was stopped, and the patient showed no evidence of relapse at 4 months after resection. In this case, larotrectinib was obtained using Single Patient Expanded Access under the FDA. In this paper, we also discuss the issues faced while accessing unapproved drugs in the precision medicine era in Japan.
要旨 症例は8歳,女児。6歳時に右上腕に発生した軟部肉腫の腫瘍切除術が行われたが,16か月後に局所再発を起こした。初発時の腫瘍検体を用いたRNA seqデータより LMNA-NTRK1 融合遺伝子が検出されていたことから,larotrectinibの治験への参加を検討した。しかし当時小児を対象とした国内での治験が行われておらず,院内倫理委員会での承認を経て,米国食品医薬品局(FDA)のSingle Patient Expanded Access制度に申請し,larotrectinibによる治療を開始した。投薬開始3か月後には画像上の完全寛解(complete remission: CR)が得られ,さらに6か月治療を継続した後,試験切除を行い組織学的CR(pCR)を確認した。今回この症例の治療経過を報告するとともに,今後日本でも普及していくゲノム医療により同定されたまれなドライバー変異に対する治療法へのアクセス方法の課題について考察を加えて報告する。