Case Report: Lenvatinib plus osimertinib treated a metastatic hilar cholangiocarcinoma patient harboring EGFR mutation
- 1Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- 2Liver Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- 3Department of Hepatobiliary Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital
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.
Case 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.
Conclusion: 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.
Related
- Coexistence of Clonally Unrelated Acute Myeloid Leukemia Harboring CBFB::MYH11 and Lymphoplasmacytic Lymphoma Harboring MYD88 L252P Mutation
- Lenvatinib plus pembrolizumab in pretreated metastatic B3 thymoma and thymic carcinoma (PECATI): a single-arm, phase 2 trial
- Pemigatinib for Unresectable or Metastatic Cholangiocarcinoma With Fibroblast Growth Factor Receptor–2 Rearrangement: Results From the Phase III FIGHT-302 Trial
- Two-year dynamic risk stratification and adjuvant radioiodine efficacy in initial non-distant metastatic papillary thyroid carcinoma harboring TERT promoter mutations
- 1076 Patient-derived organoids reveal tumor-restricted noncanonical HLA-I antigen candidates in low mutation burden metastatic melanoma
BibTeX
@article{wang2026case,
title = {{Case Report: Lenvatinib plus osimertinib treated a metastatic hilar cholangiocarcinoma patient harboring EGFR mutation}},
author = {Peng Wang and Chentao Zou and Wendi Liu and Jiangli Xu and Hui Wang and Shisan Bao and Huabang Zhou},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1949186},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1949186/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Case Report: Lenvatinib plus osimertinib treated a metastatic hilar cholangiocarcinoma patient harboring EGFR mutation
AU - Peng Wang
AU - Chentao Zou
AU - Wendi Liu
AU - Jiangli Xu
AU - Hui Wang
AU - Shisan Bao
AU - Huabang Zhou
PY - 2026
DA - 2026/10/22
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1949186
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1949186/full
AB - 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. Case 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. Conclusion: 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.
SN - 1664-3224
ER -