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Open Access 01-11-2024 | Cytostatic Therapy | Research

Efficacy of durvalumab plus chemotherapy in advanced biliary duct cancer and biomarkers exploration

Authors: Yunxin Lu, Yin Jin, Furong Liu, Zixian Wang, Wen Zhou, Yang Zhang, Bing Bai, Yun Wang, Zhiqiang Wang, Man Nie, Huiyan Luo, Xiaoli Wei, Chuqiao Liang, Guifang Guo, Miaozhen Qiu, Jianwen Chen, Yu Liu, Shengping Li, Yuhong Li, Fenghua Wang, Feng Wang, Peidong Chi, Dongsheng Zhang

Published in: Cancer Immunology, Immunotherapy | Issue 11/2024

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Abstract

Background

The anti-PD-L1 antibody durvalumab has been approved for use in first-line advanced biliary duct cancer (ABC). So far, predictive biomarkers of efficacy are lacking.

Methods

ABC patients who underwent gemcitabine-based chemotherapy with or without durvalumab were retrospectively enrolled, and their baseline clinical pathological indices were retrieved from medical records. Overall (OS) and progression free survival (PFS) were calculated and analyzed. The levels of peripheral biomarkers from 48 patients were detected with assay kits including enzyme-linked immunosorbent assay. Genomic alterations in 27 patients whose tumor tissues were available were depicted via targeted next-generation sequencing.

Results

A total of 186 ABC patients met the inclusion criteria between January 2020 and December 2022 were finally enrolled in this study. Of these, 93 patients received chemotherapy with durvalumab and the rest received chemotherapy alone. Durvalumab plus chemotherapy demonstrated significant improvements in PFS (6.77 vs. 4.99 months; hazard ratio 0.65 [95% CI 0.48–0.88]; P = 0.005), but not OS (14.29 vs. 13.24 months; hazard ratio 0.91 [95% CI 0.62–1.32]; P = 0.608) vs. chemotherapy alone in previously untreated ABC patients. The objective response rate (ORR) in patients receiving chemotherapy with and without durvalumab was 19.1% and 7.8%, respectively. Pretreatment sPD-L1, CSF1R and OPG were identified as significant prognosis predictors in patients receiving durvalumab. ADGRB3 and RNF43 mutations were enriched in patients who responded to chemotherapy plus durvalumab and correlated with superior survival.

Conclusion

This retrospective real-world study confirmed the clinical benefit of durvalumab plus chemotherapy in treatment-naïve ABC patients. Peripheral sPD-L1 and CSF1R are promising prognostic biomarkers for this therapeutic strategy. Presence of ADGRB3 or RNF43 mutations could improve the stratification of immunotherapy outcomes, but further studies are warranted to explore the underlying mechanisms.
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Literature
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Metadata
Title
Efficacy of durvalumab plus chemotherapy in advanced biliary duct cancer and biomarkers exploration
Authors
Yunxin Lu
Yin Jin
Furong Liu
Zixian Wang
Wen Zhou
Yang Zhang
Bing Bai
Yun Wang
Zhiqiang Wang
Man Nie
Huiyan Luo
Xiaoli Wei
Chuqiao Liang
Guifang Guo
Miaozhen Qiu
Jianwen Chen
Yu Liu
Shengping Li
Yuhong Li
Fenghua Wang
Feng Wang
Peidong Chi
Dongsheng Zhang
Publication date
01-11-2024
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 11/2024
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-024-03796-1

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