Scattolin Daniela, Scagliori Elena, Scapinello Antonio, Fantin Alberto, Guarneri Valentina, Pasello Giulia
Medical Oncology 2, Veneto Institute of Oncology (IOV), IRCCS, Padova, Italy.
Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
Front Oncol. 2023 Jul 10;13:1201599. doi: 10.3389/fonc.2023.1201599. eCollection 2023.
Rearranged during transfection () gene rearrangements occur in 1%-2% of non-small cell lung cancer (NSCLC). Because of the results of the study LIBRETTO-001, selpercatinib has been approved as the first-line treatment for patients with fusion-positive advanced NSCLC. Selpercatinib demonstrated to be well tolerated. Despite this, gastrointestinal adverse events (AEs) are frequently reported, and no clinical-radiological and endoscopic features and their impact in terms of treatment discontinuations, interruptions, and dose reductions have been described so far.
A 37-year-old never-smoker woman was treated in our institution with selpercatinib for a fusion-positive NSCLC. After 9 months of treatment, the patient referred abdominal pain of grade (G) 2, associated with nausea of G2, bilious vomiting of G3, and weight loss of G1. At computed tomography scan, the presence of important bowel wall thickening, free ascitic fluid, mesenteric congestion, and stranding was detected. The patient underwent an anterograde enteroscopy extended to jejunum with detection of lymphocytic duodenitis with sub-mucosal edema. Selpercatinib treatment was temporary interrupted with complete resolution of the symptoms and then re-administered with dose reduction, without relapsed of the gastrointestinal toxicity after 120 days.
To our knowledge, this is the first case report of a patient with NSCLC treated with selpercatinib outside a clinical study who developed severe gastrointestinal toxicity characterized by small bowel edema and lymphocytic duodenitis, leading to treatment interruption and dose reduction. The gastrointestinal AE has been described by a radiological, endoscopic, and histopathological point of view. Further investigations are needed to better identify pathological mechanisms of gastrointestinal toxicity for an appropriate AE management.
转染期间重排（RET）基因重排在1%-2%的非小细胞肺癌（NSCLC）中发生。基于LIBRETTO-001研究结果，塞尔帕替尼已被批准作为RET融合阳性晚期NSCLC患者的一线治疗药物。塞尔帕替尼耐受性良好。尽管如此，胃肠道不良事件（AE）仍经常被报道，且目前尚无关于其临床-放射学和内镜特征以及它们对治疗中断、暂停和剂量减少影响的描述。
一名37岁从不吸烟的女性在我们机构接受塞尔帕替尼治疗RET融合阳性NSCLC。治疗9个月后，患者出现2级腹痛，伴有2级恶心、3级胆汁性呕吐和1级体重减轻。在计算机断层扫描中，检测到肠壁明显增厚、游离腹水、肠系膜充血和条索状改变。患者接受了延伸至空肠的顺行肠镜检查，发现淋巴细胞性十二指肠炎症伴黏膜下水肿。塞尔帕替尼治疗暂时中断，症状完全缓解，然后减量重新给药，120天后胃肠道毒性未复发。
据我们所知，这是首例在临床研究之外接受塞尔帕替尼治疗的NSCLC患者发生严重胃肠道毒性的病例报告，其特征为小肠水肿和淋巴细胞性十二指肠炎症，导致治疗中断和剂量减少。从放射学、内镜和组织病理学角度描述了胃肠道AE。需要进一步研究以更好地确定胃肠道毒性的病理机制，从而进行适当的AE管理。
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