{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:31:09Z","timestamp":1786325469837,"version":"build-2736575974"},"reference-count":28,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Based on the demonstrated survival benefits of gemcitabine plus cisplatin (GemCis) therapy in the TOPAZ-1 and KEYNOTE-966 trials, GemCis plus immune checkpoint inhibitor (ICI) therapy has become a standard first-line treatment for unresectable biliary tract cancer. However, its safety and efficacy in elderly patients and those requiring biliary drainage remain insufficiently evaluated in real-world practice. We aimed to evaluate the efficacy and safety of GemCis plus ICI therapy, with a focus on elderly patients and those requiring biliary drainage. Methods: We retrospectively analyzed the clinical characteristics of patients with unresectable biliary tract cancer treated with GemCis plus ICI at our institution between April 2022 and September 2025. Progression-free survival (PFS) was analyzed using the Kaplan\u2013Meier method, and prognostic factors were examined using Cox proportional hazards models. PFS and immune-related adverse events (irAEs) were compared between durvalumab and pembrolizumab. Results: Of the 51 patients diagnosed with unresectable biliary tract cancer during the observation period, 26 (51.0%) received GemCis plus ICI therapy. The median age was 73 years (range, 46\u201383 years), and 15 (57.7%) patients were male. Distant metastases were present in 22 patients (84.6%), and biliary drainage was performed in 15 (57.7%). The primary tumor sites were intrahepatic cholangiocarcinoma (n = 8), perihilar cholangiocarcinoma (n = 6), gallbladder cancer (n = 11), and cancer of unknown primary origin (n = 1). The ICIs used were durvalumab in 18 patients and pembrolizumab in eight patients. The median follow-up period was 214 days (range, 30\u20131114). The response rate was 28.6%, the disease control rate was 90.5%, and the transition rate to ICI maintenance therapy was 29.2%. IrAEs occurred in six patients (23.1%), with a significantly higher frequency in the pembrolizumab group than in the durvalumab group (50.0% vs. 11.1%). The median PFS was 8.2 months in the durvalumab group and 8.9 months in the pembrolizumab group, with no significant difference (p = 0.88). Multivariate analysis incorporating age, performance status, metastatic burden, and liver function confirmed that age \u2265 75 years remained the only independent predictor of shorter PFS (HR 5.62; 95% CI, 1.35\u201323.4; p = 0.02), whereas ICI regimen and biliary drainage were not significant prognostic factors. Conclusions: In clinical practice, GemCis plus ICI therapy showed no statistically significant difference in efficacy between ICI regimens in this small cohort, although this comparison was not statistically powered. Given the exploratory nature of these findings, the lower incidence of immune-related adverse events (irAEs) observed in the durvalumab group should be interpreted with caution. Age \u2265 75 years was associated with shorter PFS. Careful patient selection is warranted when considering GemCis plus ICI therapy in elderly patients with biliary tract cancer.<\/jats:p>","DOI":"10.3390\/cancers18162555","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:20:03Z","timestamp":1786324803000},"page":"2555","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real-World Efficacy and Safety of Gemcitabine, Cisplatin, Plus Immune Checkpoint Inhibitors in Biliary Tract Cancer: A Retrospective Analysis"],"prefix":"10.3390","volume":"18","author":[{"given":"Mai","family":"Kitahara","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2290-9373","authenticated-orcid":false,"given":"Kei","family":"Saito","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Oki","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Kuniyoshi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6838-9774","authenticated-orcid":false,"given":"Shuzo","family":"Nomura","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0843-3065","authenticated-orcid":false,"given":"Mariko","family":"Fujisawa","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2355-7309","authenticated-orcid":false,"given":"Hirofumi","family":"Kogure","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102688","DOI":"10.1016\/j.canep.2024.102688","article-title":"Prognosis related to treatment plan in patients with biliary tract cancer: A nationwide database study","volume":"93","author":"Fristrup","year":"2024","journal-title":"Cancer Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1093\/oncolo\/oyac150","article-title":"Temporal Changes in Cholangiocarcinoma Incidence and Mortality in the United States from 2001 to 2017","volume":"27","author":"Javle","year":"2022","journal-title":"Oncologist"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1056\/NEJMoa0908721","article-title":"Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer","volume":"362","author":"Valle","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/sj.bjc.6605779","article-title":"Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: A comparative multicentre study in Japan","volume":"103","author":"Okusaka","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1002\/jhbp.1219","article-title":"Randomized phase III study of gemcitabine, cisplatin plus S-1 versus gemcitabine, cisplatin for advanced biliary tract cancer (KHBO1401-MITSUBA)","volume":"30","author":"Ioka","year":"2023","journal-title":"J. Hepato-Biliary-Pancreat. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7229","DOI":"10.3390\/curroncol30080524","article-title":"Safety and Effectiveness of Chemotherapy in Elderly Biliary Tract Cancer Patients","volume":"30","author":"Okamoto","year":"2023","journal-title":"Curr. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1038\/s41598-021-04550-8","article-title":"The clinical outcomes of combination chemotherapy in elderly patients with advanced biliary tract cancer: An exploratory analysis of JCOG1113","volume":"12","author":"Yamada","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/j.1477-2574.2011.00431.x","article-title":"Effect of biliary drainage on chemotherapy in patients with biliary tract cancer: An exploratory analysis of the BT22 study","volume":"14","author":"Fukutomi","year":"2012","journal-title":"HPB"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kurihara, E., Kakizaki, S., Ijima, M., Hatanaka, T., Kubo, N., Suzuki, Y., Yasuoka, H., Hoshino, T., Naganuma, A., and Tani, N. (2025). Efficacy and Safety of the Combination of Durvalumab Plus Gemcitabine and Cisplatin in Patients with Advanced Biliary Tract Cancer: A Real-World Retrospective Cohort Study. Biomedicines, 13.","DOI":"10.20944\/preprints202506.0060.v1"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"EVIDoa2200015","DOI":"10.1056\/EVIDoa2200015","article-title":"Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer","volume":"1","author":"Oh","year":"2022","journal-title":"NEJM Evid."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1016\/S0140-6736(23)00727-4","article-title":"Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): A randomised, double-blind, placebo-controlled, phase 3 trial","volume":"401","author":"Kelley","year":"2023","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/S2468-1253(24)00095-5","article-title":"Durvalumab or placebo plus gemcitabine and cisplatin in participants with advanced biliary tract cancer (TOPAZ-1): Updated overall survival from a randomised phase 3 study","volume":"9","author":"Oh","year":"2024","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ejca.2006.11.004","article-title":"International Society of Geriatric Oncology (SIOG) recommendations for the adjustment of dosing in elderly cancer patients with renal insufficiency","volume":"43","author":"Lichtman","year":"2007","journal-title":"Eur. J. Cancer"},{"key":"ref_14","first-page":"3461","article-title":"Management of hepatotoxicity of chemotherapy and targeted agents","volume":"11","author":"Mudd","year":"2021","journal-title":"Am. J. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"17588359251344013","DOI":"10.1177\/17588359251344013","article-title":"Management of biliary tract cancers in elderly patients: A French multicenter retrospective study (PRONOBIL-ACABi)","volume":"17","author":"Valery","year":"2025","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1038\/bjc.2015.120","article-title":"The impact of comprehensive geriatric assessment interventions on tolerance to chemotherapy in older people","volume":"112","author":"Kalsi","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1111\/jgh.15066","article-title":"The impact of age and comorbidity in advanced or recurrent biliary tract cancer receiving palliative chemotherapy","volume":"35","author":"Takahara","year":"2020","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Crespin, A., Le Bescop, C., de Gunzburg, J., Vitry, F., Zalcman, G., Cervesi, J., and Bandinelli, P.-A. (2023). A systematic review and meta-analysis evaluating the impact of antibiotic use on the clinical outcomes of cancer patients treated with immune checkpoint inhibitors. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1075593"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Alotaibi, F.M., Albalawi, I.A.S., Anis, A.M., Alotaibi, H., Khashwayn, S., Alshammari, K., and Al-Tawfiq, J.A. (2024). The impact of antibiotic use in gastrointestinal tumors treated with immune checkpoint inhibitors: Systematic review and meta-analysis. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1415093"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhang, L., Jin, Q., Chai, D., Kuang, T., Li, C., Guan, Y., Liu, L., Wang, W., and Deng, W. (2022). The correlation between probiotic use and outcomes of cancer patients treated with immune checkpoint inhibitors. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.937874"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lopes, S., Pabst, L., Dory, A., Klotz, M., Gourieux, B., Michel, B., and Mascaux, C. (2023). Do proton pump inhibitors alter the response to immune checkpoint inhibitors in cancer patients? A meta-analysis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1070076"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1007\/s00262-022-03363-6","article-title":"Effect of metformin on outcomes of patients treated with immune checkpoint inhibitors: A retrospective cohort study","volume":"72","author":"Chiang","year":"2023","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ejca.2021.12.024","article-title":"Renin\u2013angiotensin\u2013aldosterone system inhibitors and survival in patients with hypertension treated with immune checkpoint inhibitors","volume":"163","author":"Drobni","year":"2022","journal-title":"Eur. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1200\/OP-24-00583","article-title":"Concomitant Statin Use and Survival in Patients with Cancer on Immune Checkpoint Inhibitors: A Meta-Analysis","volume":"21","author":"Liao","year":"2025","journal-title":"JCO Oncol. Pract."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Tang, Q., Chen, Y., Li, X., Long, S., Shi, Y., Yu, Y., Wu, W., Han, L., and Wang, S. (2022). The role of PD-1\/PD-L1 and application of immune-checkpoint inhibitors in human cancers. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.964442"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s00262-024-03869-1","article-title":"Differences in immune-related toxicity between PD-1 and PD-L1 inhibitors: A retrospective cohort study in patients with advanced cancer","volume":"74","author":"Ladjevardi","year":"2024","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s12094-020-02397-5","article-title":"Anti-PD-1\/L1-associated immune-related adverse events as harbinger of favorable clinical outcome: Systematic review and meta-analysis","volume":"23","author":"Park","year":"2021","journal-title":"Clin. Transl. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1093\/jjco\/hyae067","article-title":"The correlation between immune-related adverse events and efficacy of immune checkpoint inhibitors","volume":"54","author":"Fukushima","year":"2024","journal-title":"Jpn. J. Clin. Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/16\/2555\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:25:56Z","timestamp":1786325156000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/16\/2555"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,9]]},"references-count":28,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cancers18162555"],"URL":"https:\/\/doi.org\/10.3390\/cancers18162555","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,9]]}}}