{
  "abstract": "Background Biliary tract cancer (BTC) is an aggressive malignancy with limited treatment options and a poor prognosis. Although immune checkpoint inhibitors combined with chemotherapy have improved patient outcomes, their toxicity remains concerning. This phase II multicenter trial evaluated the efficacy and safety of pembrolizumab plus lenvatinib with a reduced-dose gemcitabine and oxaliplatin (GEMOX) regimen as a first-line therapy for advanced BTC.Methods 60 patients with unresectable or metastatic BTC were enrolled from five centers in China. Patients received pembrolizumab (200 mg, every 3 weeks), lenvatinib (8 or 12 mg daily), and modified GEMOX (gemcitabine 1000 mg/m² and oxaliplatin 85 mg/m² on day 1 of each 3-week cycle) for 6–8 cycles, followed by maintenance with pembrolizumab and lenvatinib. The primary endpoint was objective response rate (ORR), and the secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.Results At a median follow-up of 16.0 months, the ORR (complete response 5.0%, partial response (PR) 50.0%) and disease control rate were 55.0% and 93.3%, respectively. The median PFS and OS were 12.5 months (95% CI 7.93 to 16.3), and 19.5 months (95% CI 17.97 to not estimable), respectively. Elevated baseline CA19-9 (>37 U/mL) and carcinoembryonic antigen levels (>5 ng/mL) were independently associated with poor OS and PFS, respectively. The regimen showed manageable toxicity, with 95% of patients experiencing treatment-emergent adverse events (AEs), mostly grades 1–2; grade 3–4 AEs occurred in 65% of patients, with no treatment-related deaths. Immune-related AEs occurred in 11.7% of the patients and were predominantly mild.Conclusions Pembrolizumab plus lenvatinib with reduced-dose GEMOX demonstrated promising efficacy and a favorable safety profile in advanced BTC, suggesting that chemotherapy de-escalation may optimize the efficacy–toxicity balance. Further randomized studies are warranted to confirm these findings and refine biomarker-based treatment selections.",
  "authors": [
    {
      "affiliations": [
        "Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China"
      ],
      "name": "Mingjian Piao"
    },
    {
      "affiliations": [
        "Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China"
      ],
      "name": "Chengjie Li"
    },
    {
      "affiliations": [
        "Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China"
      ],
      "name": "Shuofeng Li"
    },
    {
      "affiliations": [
        "Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China"
      ],
      "name": "Nan Zhang"
    },
    {
      "affiliations": [
        "Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China"
      ],
      "name": "Jiongyuan Li"
    },
    {
      "affiliations": [
        "Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China"
      ],
      "name": "Xu Luo"
    },
    {
      "affiliations": [
        "Faculty of Hepatopancreatobiliary Surgery, The First Medical Center of PLA General Hospital, Beijing, People's Republic of China"
      ],
      "name": "Rong Liu"
    },
    {
      "affiliations": [
        "Faculty of Hepatopancreatobiliary Surgery, The First Medical Center of PLA General Hospital, Beijing, People's Republic of China"
      ],
      "name": "Fei Wang"
    },
    {
      "affiliations": [
        "Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China"
      ],
      "name": "Xiangde Shi"
    },
    {
      "affiliations": [
        "Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China"
      ],
      "name": "Chao Liu"
    },
    {
      "affiliations": [
        "Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China"
      ],
      "name": "Guang Tan"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery, The Fifth Medical Center of PLA General Hospital, Beijing, People's Republic of China"
      ],
      "name": "Zhenyu Zhu"
    },
    {
      "affiliations": [
        "Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China"
      ],
      "name": "Xiaobo Yang"
    },
    {
      "affiliations": [
        "Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China"
      ],
      "name": "Haitao Zhao"
    }
  ],
  "title": "Efficacy and safety of pembrolizumab, lenvatinib, and reduced-dose gemcitabine/oxaliplatin as initial treatment for advanced biliary tract cancer: a multicenter, single-arm, prospective, phase II study",
  "uid": "73aabb5b-c467-5926-abd7-4f9ebe47b2eb"
}