{
  "abstract": "Background: Hilar cholangiocarcinoma (hCCA) is an aggressive malignancy with limited therapeutic options and poor prognosis, particularly in patients with unresectable or metastatic disease. Although immune checkpoint inhibitors and targeted therapies have improved outcomes, resistance remains a major challenge. Here, we report a case of metastatic hCCA with possible lenvatinib resistance managed by sequential molecular-guided therapy.\n\nCase presentation: A 57-year-old man was diagnosed with stage IVB hCCA with extensive distant metastases. As curative surgery was not feasible, gemcitabine plus S-1 chemotherapy was initiated but discontinued after two cycles due to grade 3 myelosuppression. Given high PD-L1 expression (combined positive score = 20), treatment was switched to tislelizumab combined with lenvatinib and S-1, resulting in a partial response of the primary tumor and metastatic lesions. After approximately six months, isolated progression of pulmonary metastases occurred. Retrospective molecular testing of the pretreatment lung biopsy identified an EGFR exon 19 deletion (p.E746_A750del), prompting subsequent EGFR-targeted therapy. Addition of gefitinib achieved marked regression of pulmonary lesions, however, severe drug-related urinary tract inflammation required discontinuation of gefitinib and tislelizumab. Following subsequent progression on lenvatinib monotherapy, treatment was changed to osimertinib plus lenvatinib, resulting in renewed regression of pulmonary metastases. The patient remained on maintenance therapy with sustained disease control and an overall survival exceeding four years.\n\nConclusion: This case illustrates how molecular reassessment at disease progression can guide subsequent treatment decisions in advanced hCCA. EGFR inhibition may provide clinical benefit in selected patients with lenvatinib-resistant disease, warranting further investigation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine",
    "Liver Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine",
    "Department of Hepatobiliary Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital"
  ],
  "article_type": "case report",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Peng Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Chentao Zou"
    },
    {
      "affs": [
        2
      ],
      "name": "Wendi Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Jiangli Xu"
    },
    {
      "affs": [
        2
      ],
      "name": "Hui Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Shisan Bao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Huabang Zhou"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3n8gdgd2j7p4k.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1949186",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735606/",
  "id": "3n8gdgd2j7p4k",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1949186/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Case Report"
    ],
    [
      "openalex",
      "2746|Cholangiocarcinoma and Gallbladder Cancer Studies"
    ]
  ],
  "openalex": "W7223187746",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1949186/pdf",
  "pmcid": "PMC13735606",
  "pmid": "42991293",
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/3n8gdgd2j7p4k.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1949186",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1949186/full"
    },
    {
      "first_seen": "2026-11-09T12:21:15Z",
      "native_id": "PMC13735606",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1949186"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Cholangiocarcinoma and Gallbladder Cancer Studies",
      "subfield": "surgery"
    }
  ],
  "title": "Case Report: Lenvatinib plus osimertinib treated a metastatic hilar cholangiocarcinoma patient harboring EGFR mutation",
  "title_text": "Case Report: Lenvatinib plus osimertinib treated a metastatic hilar cholangiocarcinoma patient harboring EGFR mutation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:15Z",
  "url": "https://research.draconitic.com/paper/3n8gdgd2j7p4k",
  "venue": "Frontiers in Immunology",
  "versions": []
}