Supplementary Material for: Sustained clinical response to ivosidenib in previously treated patients with advanced intrahepatic cholangiocarcinoma harboring an IDH1 R132 mutation: two case reports

Introduction. Patients with progressing intrahepatic cholangiocarcinoma (iCCA) harboring an isocitrate dehydrogenase 1 (IDH1) mutation who received ivosidenib showed a median progression-free survival benefit of 1.3 months compared to placebo in the Phase 3 ClarIDHy trial.
Case Presentations. We describe two consecutive patients with previously treated unresectable and metastatic iCCA harboring an IDH1 R132 mutation who achieved durable clinical responses with ivosidenib 500 mg once daily for >12 months until disease progression. In 1 case with a mixed response, a single progressive liver metastasis was additionally treated locally with interstitial brachytherapy while ivosidenib was continued until further progression. Ivosidenib therapy resulted in long-term disease control with progression-free survival of 20 and 13 months, respectively. The duration of treatment with ivosidenib was 26 and 13 months, respectively, with no relevant side effects.
Conclusion. Patients with unresectable or metastatic IDH1 mutated iCCA can achieve sustained clinical responses for >12 months with ivosidenib. No new safety signals were observed during long-term treatment with ivosidenib.

引言。在III期临床试验ClarIDHy中，携带异柠檬酸脱氢酶1（isocitrate dehydrogenase 1, IDH1）突变的进展性肝内胆管癌（intrahepatic cholangiocarcinoma, iCCA）患者接受艾伏尼布（ivosidenib）治疗后，相较安慰剂组，中位无进展生存期获益达1.3个月。
病例报告。本文报告2例经治的携带IDH1 R132突变的不可切除转移性肝内胆管癌患者，均接受每日一次500mg艾伏尼布治疗，获得持久临床应答，治疗持续超过12个月直至疾病进展。其中1例呈现混合应答，在继续接受艾伏尼布治疗直至疾病再次进展的同时，对单发进展性肝转移灶追加了局部组织间近距离放射治疗。艾伏尼布治疗实现了长期疾病控制，患者的无进展生存期分别为20个月和13个月，艾伏尼布治疗时长分别为26个月和13个月，未观察到相关不良反应。
结论。携带IDH1突变的不可切除或转移性肝内胆管癌患者，接受艾伏尼布治疗可获得超过12个月的持续临床应答。长期接受艾伏尼布治疗期间未观察到新的安全性信号。