艾伏西尼布治疗IDH1突变型胆管癌——当前证据综述及一例显示持久疾病控制的病例报告。
完整摘要 · 中文译文
背景：胆管癌（CCA）是分子谱分析显著扩展了治疗格局并促进精准肿瘤学融入常规临床实践的恶性肿瘤之一。约40%的患者中可识别出潜在可操作的分子改变，其中异柠檬酸脱氢酶1（IDH1）基因突变是CCA中最常见且特征最明确的分子改变之一。 目的：旨在总结关于艾伏尼布在晚期IDH1突变型CCA患者中疗效和安全性的当前证据，并介绍一例尽管最初面临重大治疗可及性障碍但仍实现异常持久疾病控制的患者。 结果：在III期ClarIDHy试验中，艾伏尼布在既往接受过治疗的IDH1突变型CCA患者中显示出无进展生存期的统计学显著改善。经交叉调整的最终总生存分析也证实了总生存获益。这些发现随后得到多项前瞻性和回顾性真实世界研究的支持，这些研究显示了相当的疗效、高疾病控制率和良好的安全性特征。所介绍的病例展示了在艾伏尼布治疗期间持续超过25个月的持久疾病控制，同时保持了极佳的生活质量。 结论：艾伏尼布是携带IDH1 R132突变的晚期CCA二线及后续治疗的标准治疗选择。最佳患者 管理需要通过对分子改变的全面分子分析早期识别这种分子改变，并消除那些持续限制符合条件的患者及时获得靶向治疗的障碍。
完整摘要 · 英文原文
BACKGROUND: Cholangiocarcinoma (CCA) is one of the malignancies in which molecular profiling has substantially expanded the therapeutic landscape and facilitated the implementation of precision oncology into routine clinical practice. Potentially actionable molecular alterations are identified in approximately 40% of patients, with mutations in the isocitrate dehydrogenase 1 (IDH1) gene representing one of the most common and best-characterized molecular alterations in CCA. AIM: The aim is to summarize current evidence regarding the efficacy and safety of ivosidenib in patients with advanced IDH1-mutated CCA and to present the case of a patient who achieved exceptionally durable disease control despite initially facing substantial barriers to treatment access. RESULTS: In the phase III ClarIDHy trial, ivosidenib demonstrated statistically significant improvement in progression-free survival in patients with previously treated IDH1-mutated CCA. The final overall survival analysis, adjusted for crossover, also confirmed an overall survival benefit. These findings have subsequently been supported by multiple prospective and retrospective real-world studies demonstrating comparable efficacy, high disease control rates, and a favorable safety profile. The presented case illustrates durable disease control lasting more than 25 months during ivosidenib treatment while maintaining an excellent quality of life. CONCLUSION: Ivosidenib represents the standard treatment option in the second and subsequent lines of therapy for advanced CCA harboring an IDH1 R132 mutation. Optimal patient management requires early identification of this molecular alteration through comprehensive molecular profiling and removal of barriers that continue to limit timely access to targeted therapy for eligible patients.