Sadagopan Narayanan, Wang Hongkun, Yin Chao, Weinberg Benjamin Adam, Noel Marcus Smith, Mukherji Reetu, Geng Xue, Marshall John Lindsay, He Aiwu Ruth
Lombardi Comprehensive Cancer Center, MedStar Georgetown University Medical Center, 3800 Reservoir Rd NW, Washington, DC, 20007, USA.
Georgetown University, Department of Biostatistics, Bioinformatics and Biomathematics, 3700 O St NW, Washington, DC, 20057, USA.
NPJ Precis Oncol. 2025 Jul 8;9(1):229. doi: 10.1038/s41698-025-01009-1.
Effective second-line treatment for advanced biliary tract cancer (BTC) remains an unmet need. BTC often presents with homologous recombination repair (HRR) pathway deficiencies and IDH1/IDH2 mutations which suggest responsiveness to Poly (ADP-ribose) polymerase inhibitors. Thirteen patients were enrolled in our open-label, single-site phase II study of pembrolizumab and olaparib in the second-line setting and beyond for patients with advanced BTC. The objective response rate was 15.4% and the disease control rate was 53.8%. The median progression-free survival (PFS) was 5.45 months (95% CI 1.25-7.82), and the median overall survival was 7.21 months (95% CI 4.5-13.8). Both patients with IDH1 mutations and 2 of the 4 patients with HRR mutations achieved a PFS of at least 7.5 months. All BTC patients do not appear to benefit from pembrolizumab plus olaparib, but those with HRR deficiencies and/or IDH mutations may benefit although it would now represent a rechallenge with immunotherapy. Trial registration: NCT04306367, date of registration 3/10/2020.
晚期胆管癌（BTC）的有效二线治疗仍然是未满足的需求。BTC常表现出同源重组修复（HRR）途径缺陷和IDH1/IDH2突变，提示对聚（ADP-核糖）聚合酶抑制剂有反应。13名患者参加了我们在二线及以上治疗晚期BTC患者的帕博利珠单抗和奥拉帕利开放标签、单中心II期研究。客观缓解率为15.4%，疾病控制率为53.8%。中位无进展生存期（PFS）为5.45个月（95%CI 1.25-7.82），中位总生存期为7.21个月（95%CI 4.5-13.8）。IDH1突变患者和4例HRR突变患者中的2例均实现了至少7.5个月的PFS。并非所有BTC患者似乎都能从帕博利珠单抗加奥拉帕利中获益，但那些存在HRR缺陷和/或IDH突变的患者可能会获益，尽管这现在意味着再次接受免疫治疗。试验注册：NCT04306367，注册日期2020年10月3日。
