Reimann Patrick, Mavroeidi Ilektra-Antonia, Burghofer Jonathan, Taghizadeh Hossein, Webersinke Gerald, Kasper Stefan, Schreil Georg, Morariu Darius, Reichinger Andreas, Baba Hideo Andreas, Kirchweger Patrick, Schuler Martin, Djanani Angela, Prager Gerald W, Rumpold Holger, Benda Magdalena, Schneider Eva-Maria, Mink Sylvia, Winder Thomas, Doleschal Bernhard
Department of Internal Medicine II, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.
Private University of the Principality of Liechtenstein, Triesen, Principality of Liechtenstein.
Cancer Immunol Immunother. 2024 Oct 3;73(12):251. doi: 10.1007/s00262-024-03842-y.
This study assesses the effectiveness of durvalumab with platinum and gemcitabine for biliary tract cancers (BTC). It aims to confirm the TOPAZ-1 trial results in a real-world context and explore the link between BTC molecular profiles and patient outcomes.
A retrospective analysis was conducted on 102 BTC patients treated with durvalumab, platinum, and gemcitabine at five cancer centers in Austria and one in Germany from 2022 to 2024. Molecular profiling used targeted DNA and RNA assays. Clinical endpoints, including progression-free survival (PFS) and overall survival (OS), were assessed using log-rank tests and Cox regression, with correlations to second-line molecular-targeted therapies.
Among 102 patients, 60.8% had intrahepatic cholangiocarcinoma. The treatment achieved a disease control rate of 71.57% and an overall response rate of 35.11%. Median PFS was 6.51 months, and OS was 13.61 months. Patients under 65 had significantly better OS. Alterations in chromatin remodeling or homologous recombination repair genes were not predictive of survival benefit (HR: 0.45; p = 0.851 and HR: 1.63; p = 0.26, respectively). Patients with molecular-informed second-line therapy showed a trend toward survival benefit (HR: 0.23; p = 0.052).
This study confirms the phase 3 trial results of durvalumab with platinum and gemcitabine, providing a substantial real-world dataset with detailed molecular characterization. No specific patient subgroup showed a markedly better response to durvalumab based on conventional NGS panels. Further research is needed to explore the link between immunotherapy responses and molecular subgroups.
本研究评估度伐利尤单抗联合铂类和吉西他滨治疗胆管癌（BTC）的疗效。其目的是在真实世界背景下确认TOPAZ-1试验结果，并探索BTC分子特征与患者预后之间的联系。
对2022年至2024年在奥地利的五个癌症中心和德国的一个癌症中心接受度伐利尤单抗、铂类和吉西他滨治疗的102例BTC患者进行回顾性分析。分子特征分析采用靶向DNA和RNA检测。使用对数秩检验和Cox回归评估无进展生存期（PFS）和总生存期（OS）等临床终点，并与二线分子靶向治疗进行相关性分析。
102例患者中，60.8%患有肝内胆管癌。该治疗的疾病控制率为71.57%，总缓解率为35.11%。中位PFS为6.51个月，OS为13.61个月。65岁以下患者的OS明显更好。染色质重塑或同源重组修复基因的改变不能预测生存获益（HR分别为0.45；p = 0.851和HR为1.63；p = 0.26）。接受分子指导的二线治疗的患者显示出生存获益趋势（HR：0.23；p = 0.052）。
本研究证实了度伐利尤单抗联合铂类和吉西他滨的3期试验结果，提供了一个具有详细分子特征的大量真实世界数据集。基于传统的NGS检测板，没有特定的患者亚组对度伐利尤单抗表现出明显更好的反应。需要进一步研究来探索免疫治疗反应与分子亚组之间的联系。
