49P A phase II trial of nivolumab and gemcitabine and S-1 as the first-line treatment in patients with advanced biliary tract cancer

Chiang, N-J.; Bai, L-Y.; Huang, Cheng‐Han; Chen, Shuo; Hsiao, C-F.; Shan, Y-S.; Chen, Li Fen; Mh, Chen

doi:10.1016/j.annonc.2021.08.328

Cited by 6 publications

(6 citation statements)

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“…PD-1 inhibitors, which are important components of ICIs, are increasingly used in BTC therapy [ 8 , 24 , 25 ]. Nivolumab combined with gemcitabine and tegafur chemotherapy has shown a good therapeutic effect in the first-line treatment of advanced BTC, with an ORR of 41.7% [ 24 ]. A study of PD-1 inhibitors plus lenvatinib for unresectable BTC showed an ORR of 42.1% [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy, safety, and prognostic factors of PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy as first-line treatment in advanced intrahepatic cholangiocarcinoma: a multicenter real-world study

Zhu

Yang

et al. 2023

Cancer Immunol Immunother

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Background A programmed cell death protein-1 (PD-1) inhibitor combined with lenvatinib and Gemox chemotherapy as first-line therapy demonstrated high anti-tumor activity against biliary tract cancer in phase II clinical trials. Herein, we aimed to investigate the efficacy and safety for advanced intrahepatic cholangiocarcinoma (ICC) in a multicenter real-world study. Methods Patients with advanced ICC who received PD-1 inhibitor combined with lenvatinib and Gemox chemotherapy were retrospectively screened at two medical centers. The primary endpoints were overall survival (OS) and progression-free survival (PFS), whereas the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors for survival were analyzed. Results Fifty-three patients with advanced ICC were included in this study. The median follow-up time was 13.7 (95% confidence interval (CI): 12.9–17.2) months. The median OS and PFS were 14.3 (95% CI: 11.3–NR) and 8.63 (95% CI: 7.17–11.6) months, respectively. The ORR, DCR, and clinical benefit rate were 52.8, 94.3, and 75.5%, respectively. In the multivariate analysis, the tumor burden score (TBS), tumor-node metastasis classification (TNM) stage, and PD-L1 expression were independent prognostic factors for OS and PFS. All patients experienced adverse events (AEs), 41.5% (22/53) experienced grade 3 or 4 AEs, including fatigue (8/53, 15.1%) and myelosuppression (7/53, 13.2%). No grade 5 AEs were reported. Conclusion PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy represent an effective and tolerable regimen for advanced ICC in a multicenter retrospective real-world study. TBS, TNM stage, and PD-L1 expression can be used as potential prognostic factors for OS and PFS.

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Section: Discussionmentioning

confidence: 99%

Efficacy, safety, and prognostic factors of PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy as first-line treatment in advanced intrahepatic cholangiocarcinoma: a multicenter real-world study

Zhu

Yang

et al. 2023

Cancer Immunol Immunother

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“…4d and 4e, left panel). We changed systemic therapy to nivolumab plus modi ed gemcitabine and TS-1 (NGS) every 2 weeks [13]. After NGS treatment for 3 months, the multiple metastatic lymphadenopathies obviously decreased bilateral pleural effusion improved which lasted for almost one year (Fig.…”

Section: Response Of Ebv-lelcc To Anti-pd-1 Monoclonal Antibody Treat...mentioning

confidence: 99%

The immune microenvironment features and response to immunotherapy in EBV-associated lymphoepithelioma-like cholangiocarcinoma

et al. 2022

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Background & Aims Limited data are available for tumor immune microenvironment (TIME) in Epstein-Barr virus (EBV)-associated lymphoepithelioma-like cholangiocarcinoma (EBV-LELCC), a rare subtype of intrahepatic cholangiocarcinoma (IHCC). We aimed to investigate TIME features in EBV-LELCC and the correlation between the components of TIME and the clinical outcomes.Methods Tumor tissues from Five EBV-LELCC cases con rmed through EBER in situ hybridization and ve stage-matched conventional IHCC (non-EBV IHCC) cases were collected. These samples were used to evaluate genetic alterations, TIME composition, and PD-L1 expression through ion AmpliSeq comprehensive cancer panel, PanCancer immune pro ling panel, immunohistochemistry, and immuno uorescence staining. The correlation between clinical outcomes and TIME components was analyzed in the two EBV-LELCC cases receiving anti-PD-1 treatment. ResultsThe genetic mutations identi ed in EBV-LELCC were BARD1, CD19, CD79B, EPHA5, KDM5A, MUC6, MUC16, PTEN, RECQL4, TET1, and TNFAIP3. PD-L1 was highly expressed in tumor-in ltrating immune cells, especially the T cells and macrophages. The TIME of EBV-LELCC displayed abundant immune cell in ltration with a stronger adaptive immune response. Increased Th1 cells, NK CD56 dim cells, and M1 macrophages, decreased M2 macrophages, exhausted CD8 T cell in ltration, and increased T cell activation signatures in TIME were associated with longer survival. Two patients with metastatic EBV-LELCC had good disease control after anti-PD-1 antibody treatment. A signi cantly larger TIME component made EBV-LELCCs more sensitive to immune checkpoint blockade (ICB). Conclusion A better understanding of the composition of TIME in EBV-LELCC is critical for predicting the clinical outcomes of ICB treatment. Lay Summary Epstein-Barr virus-associated lymphoepithelioma-like cholangiocarcinoma (EBV-LELCC) is a unique variant of intrahepatic cholangiocarcinoma with dense in ltration of immune cells, different genetic backgrounds, and tumor immune microenvironment (TIME). The components of TIME may predict clinical outcome in EBV-LELCC and can potentially be exploited to enhance the e cacy of immunotherapy. Patients with EBV-LELCC are good candidates for the clinical bene t from immunotherapy.

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“…. They may represent news options but need further studies (17,18). However, the NuTide:121 trial comparing cisplatin-NUC-1031, an optimized gemcitabine derivative, with CISGEM (19) was stopped prematurely in January 2022 by the study's independent data monitoring committee due to futility at interim analysis with no published results to date, despite promising results in phase 1 (20).…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Cholangiocarcinoma: what are the options in all comers and how has the advent of molecular profiling opened the way to personalised medicine ?

Roth¹,

Neuzillet²,

Sarabi³

et al. 2023

European Journal of Cancer

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49P A phase II trial of nivolumab and gemcitabine and S-1 as the first-line treatment in patients with advanced biliary tract cancer

Abstract: Background: The regimen of modified gemcitabine and S-1 (GS) is active and safe for patients with advanced biliary tract cancer (ABTC) in our previous study. Herein, we report the results of a single arm phase II of Nivolumab plus modified GS as the firstline treatment in ABTC patients.

Cited by 6 publications

References 0 publications

Efficacy, safety, and prognostic factors of PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy as first-line treatment in advanced intrahepatic cholangiocarcinoma: a multicenter real-world study

Efficacy, safety, and prognostic factors of PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy as first-line treatment in advanced intrahepatic cholangiocarcinoma: a multicenter real-world study

The immune microenvironment features and response to immunotherapy in EBV-associated lymphoepithelioma-like cholangiocarcinoma

Cholangiocarcinoma: what are the options in all comers and how has the advent of molecular profiling opened the way to personalised medicine ?

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