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Lenvatinib Plus Programmed Cell Death Protein-1 Inhibitor Beyond First-Line Systemic Therapy in Refractory Advanced Biliary Tract Cancer: A Real-World Retrospective Study in China

BACKGROUND: Currently, no second-line systemic treatment regimen has been recommended in advanced biliary tract cancer (BTC). Cumulative clinical evidence showed that systemic treatment with tyrosine kinase inhibitors (TKIs) in combination with immunotherapy may shed light on the dim clinical outcom...

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Autores principales: Shi, Changying, Li, Yulong, Yang, Cheng, Qiao, Liang, Tang, Liukang, Zheng, Yuting, Chen, Xue, Qian, Youwen, Yang, Jiamei, Wu, Dong, Xie, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364266/
https://www.ncbi.nlm.nih.gov/pubmed/35967452
http://dx.doi.org/10.3389/fimmu.2022.946861
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author Shi, Changying
Li, Yulong
Yang, Cheng
Qiao, Liang
Tang, Liukang
Zheng, Yuting
Chen, Xue
Qian, Youwen
Yang, Jiamei
Wu, Dong
Xie, Feng
author_facet Shi, Changying
Li, Yulong
Yang, Cheng
Qiao, Liang
Tang, Liukang
Zheng, Yuting
Chen, Xue
Qian, Youwen
Yang, Jiamei
Wu, Dong
Xie, Feng
author_sort Shi, Changying
collection PubMed
description BACKGROUND: Currently, no second-line systemic treatment regimen has been recommended in advanced biliary tract cancer (BTC). Cumulative clinical evidence showed that systemic treatment with tyrosine kinase inhibitors (TKIs) in combination with immunotherapy may shed light on the dim clinical outcome in advanced BTC. OBJECTIVE: The aim of this study is to evaluate the anticancer efficacy of lenvatinib plus programmed cell death protein-1 (PD-1) antibody in patients with BTC who progressed after first-line cisplatin/gemcitabine (CisGem) chemotherapy. METHODS: Patients with advanced BTCs who progressed after CisGem were recruited. A combination regimen of lenvatinib (8/12 mg daily) plus PD-1 antibody (200/240 mg injection every 3 weeks) was prescribed. Clinicopathological information and therapeutic outcome, including tumor subtypes, biomarkers, treatment duration, adverse events (AE), progression-free survival (PFS), and overall survival (OS), were recorded and estimated. RESULTS: A total of 351 patients with BTCs were reviewed and 74 were recruited eventually: 35 had intrahepatic cholangiocarcinoma (47.3%), 4 had extrahepatic cholangiocarcinoma (5.4%), and 35 had gallbladder cancer (47.3%). The median administered cycles of PD-1 antibody were 6.43 (95% CI: 5.83–7.04) cycles, and the median duration of lenvatinib medication was 21.0 weeks (95% CI: 18.04–23.93). Twenty-eight patients (37.83%) experienced detectable objective response per RECIST1.1 within a median follow-up duration of 15.0 months. The objective response rate (ORR) was 20.27% (95% CI: 10.89%–29.65%), and the disease control rate (DCR) was 71.62% (95% CI: 61.11%–82.14%). The median PFS and OS were 4.0 months (95% CI: 3.5–5.0) and 9.50 months (95% CI: 9.0–11.0), respectively. Seventy-three patients (98.64%) reported AEs and 39 (52.70%) experienced ≥grade 3 AEs. In subgroup analyses, tumoral PD-L1 expression ≥50% and tumor mutation burden (TMB) ≥2.5 Muts/Mb were associated with prolonged PFS. CONCLUSION: Lenvatinib plus PD-1 antibody treatment shows an active trend towards improving survival in patients with advanced BTCs after failure with CisGem chemotherapy. The treatment-related AEs are worthy of attention and are manageable.
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spelling pubmed-93642662022-08-11 Lenvatinib Plus Programmed Cell Death Protein-1 Inhibitor Beyond First-Line Systemic Therapy in Refractory Advanced Biliary Tract Cancer: A Real-World Retrospective Study in China Shi, Changying Li, Yulong Yang, Cheng Qiao, Liang Tang, Liukang Zheng, Yuting Chen, Xue Qian, Youwen Yang, Jiamei Wu, Dong Xie, Feng Front Immunol Immunology BACKGROUND: Currently, no second-line systemic treatment regimen has been recommended in advanced biliary tract cancer (BTC). Cumulative clinical evidence showed that systemic treatment with tyrosine kinase inhibitors (TKIs) in combination with immunotherapy may shed light on the dim clinical outcome in advanced BTC. OBJECTIVE: The aim of this study is to evaluate the anticancer efficacy of lenvatinib plus programmed cell death protein-1 (PD-1) antibody in patients with BTC who progressed after first-line cisplatin/gemcitabine (CisGem) chemotherapy. METHODS: Patients with advanced BTCs who progressed after CisGem were recruited. A combination regimen of lenvatinib (8/12 mg daily) plus PD-1 antibody (200/240 mg injection every 3 weeks) was prescribed. Clinicopathological information and therapeutic outcome, including tumor subtypes, biomarkers, treatment duration, adverse events (AE), progression-free survival (PFS), and overall survival (OS), were recorded and estimated. RESULTS: A total of 351 patients with BTCs were reviewed and 74 were recruited eventually: 35 had intrahepatic cholangiocarcinoma (47.3%), 4 had extrahepatic cholangiocarcinoma (5.4%), and 35 had gallbladder cancer (47.3%). The median administered cycles of PD-1 antibody were 6.43 (95% CI: 5.83–7.04) cycles, and the median duration of lenvatinib medication was 21.0 weeks (95% CI: 18.04–23.93). Twenty-eight patients (37.83%) experienced detectable objective response per RECIST1.1 within a median follow-up duration of 15.0 months. The objective response rate (ORR) was 20.27% (95% CI: 10.89%–29.65%), and the disease control rate (DCR) was 71.62% (95% CI: 61.11%–82.14%). The median PFS and OS were 4.0 months (95% CI: 3.5–5.0) and 9.50 months (95% CI: 9.0–11.0), respectively. Seventy-three patients (98.64%) reported AEs and 39 (52.70%) experienced ≥grade 3 AEs. In subgroup analyses, tumoral PD-L1 expression ≥50% and tumor mutation burden (TMB) ≥2.5 Muts/Mb were associated with prolonged PFS. CONCLUSION: Lenvatinib plus PD-1 antibody treatment shows an active trend towards improving survival in patients with advanced BTCs after failure with CisGem chemotherapy. The treatment-related AEs are worthy of attention and are manageable. Frontiers Media S.A. 2022-07-27 /pmc/articles/PMC9364266/ /pubmed/35967452 http://dx.doi.org/10.3389/fimmu.2022.946861 Text en Copyright © 2022 Shi, Li, Yang, Qiao, Tang, Zheng, Chen, Qian, Yang, Wu and Xie https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Shi, Changying
Li, Yulong
Yang, Cheng
Qiao, Liang
Tang, Liukang
Zheng, Yuting
Chen, Xue
Qian, Youwen
Yang, Jiamei
Wu, Dong
Xie, Feng
Lenvatinib Plus Programmed Cell Death Protein-1 Inhibitor Beyond First-Line Systemic Therapy in Refractory Advanced Biliary Tract Cancer: A Real-World Retrospective Study in China
title Lenvatinib Plus Programmed Cell Death Protein-1 Inhibitor Beyond First-Line Systemic Therapy in Refractory Advanced Biliary Tract Cancer: A Real-World Retrospective Study in China
title_full Lenvatinib Plus Programmed Cell Death Protein-1 Inhibitor Beyond First-Line Systemic Therapy in Refractory Advanced Biliary Tract Cancer: A Real-World Retrospective Study in China
title_fullStr Lenvatinib Plus Programmed Cell Death Protein-1 Inhibitor Beyond First-Line Systemic Therapy in Refractory Advanced Biliary Tract Cancer: A Real-World Retrospective Study in China
title_full_unstemmed Lenvatinib Plus Programmed Cell Death Protein-1 Inhibitor Beyond First-Line Systemic Therapy in Refractory Advanced Biliary Tract Cancer: A Real-World Retrospective Study in China
title_short Lenvatinib Plus Programmed Cell Death Protein-1 Inhibitor Beyond First-Line Systemic Therapy in Refractory Advanced Biliary Tract Cancer: A Real-World Retrospective Study in China
title_sort lenvatinib plus programmed cell death protein-1 inhibitor beyond first-line systemic therapy in refractory advanced biliary tract cancer: a real-world retrospective study in china
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364266/
https://www.ncbi.nlm.nih.gov/pubmed/35967452
http://dx.doi.org/10.3389/fimmu.2022.946861
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