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Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215)

BACKGROUND: Immunotherapy has revolutionized the treatment of cancer. However, microsatellite stable (MSS) metastatic colorectal cancer (mCRC) shows a low response to PD-1 inhibitors. Antiangiogenic therapy can enhance anti-PD-1 efficacy, but it still cannot meet clinical needs. Increasing evidence...

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Autores principales: Zhao, Wensi, Lei, Jun, Ke, Shaobo, Chen, Yuan, Xiao, Jiping, Tang, Ze, Wang, Li, Ren, Yiping, Alnaggar, Mohammed, Qiu, Hu, Shi, Wei, Yin, Lei, Chen, Yongshun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10679864/
https://www.ncbi.nlm.nih.gov/pubmed/38024475
http://dx.doi.org/10.1016/j.eclinm.2023.102315
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author Zhao, Wensi
Lei, Jun
Ke, Shaobo
Chen, Yuan
Xiao, Jiping
Tang, Ze
Wang, Li
Ren, Yiping
Alnaggar, Mohammed
Qiu, Hu
Shi, Wei
Yin, Lei
Chen, Yongshun
author_facet Zhao, Wensi
Lei, Jun
Ke, Shaobo
Chen, Yuan
Xiao, Jiping
Tang, Ze
Wang, Li
Ren, Yiping
Alnaggar, Mohammed
Qiu, Hu
Shi, Wei
Yin, Lei
Chen, Yongshun
author_sort Zhao, Wensi
collection PubMed
description BACKGROUND: Immunotherapy has revolutionized the treatment of cancer. However, microsatellite stable (MSS) metastatic colorectal cancer (mCRC) shows a low response to PD-1 inhibitors. Antiangiogenic therapy can enhance anti-PD-1 efficacy, but it still cannot meet clinical needs. Increasing evidence supported a close relationship between gut microbiome and anti-PD-1 efficacy. This study aimed to explore the efficacy and safety of the combination of fecal microbiota transplantation (FMT) and tislelizumab and fruquintinib in refractory MSS mCRC. METHODS: In the phase II trial, MSS mCRC patients were administered FMT plus tislelizumab and fruquintinib as a third-line or above treatment. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), clinical benefit rate (CBR), safety and quality of life. Feces and peripheral blood were collected for exploratory biomarker analysis. This study is registered with Chictr.org.cn, identifier ChiCTR2100046768. FINDINGS: From May 10, 2021 to January 17, 2022, 20 patients were enrolled. Median follow-up was 13.7 months. Median PFS was 9.6 months (95% CI 4.1–15.1). Median OS was 13.7 months (95% CI 9.3–17.7). Median DoR was 8.1 months (95% CI 1.7–10.6). ORR was 20% (95% CI 5.7–43.7). DCR was 95% (95% CI 75.1–99.9). CBR was 60% (95% CI 36.1–80.9). Nineteen patients (95%) experienced at least one treatment-related adverse event (TRAE). Six patients (30%) had grade 3–4 TRAEs, with the most common being albuminuria (10%), urine occult blood (10%), fecal occult blood (10%), hypertension (5%), hyperglycemia (5%), liver dysfunction (5%), hand-foot skin reaction (5%), and hypothyroidism (5%). No treatment-related deaths occurred. Responders had a high-abundance of Proteobacteria and Lachnospiraceae family and a low-abundance of Actinobacteriota and Bifidobacterium. The treatment did not change the structure of peripheral blood TCR repertoire. However, the expanded TCRs exhibited the characteristics of antigen-driven responses in responders. INTERPRETATION: FMT plus tislelizumab and fruquintinib as third-line or above treatment showed improved survival and manageable safety in refractory MSS mCRC, suggesting a valuable new treatment option for this patient population. FUNDING: This study was supported by the 10.13039/501100001809National Natural Science Foundation of China (82102954 to Wensi Zhao) and the 10.13039/501100018570Special Project of Central Government for Local Science and Technology Development of Hubei Province (ZYYD2020000169 to Yongshun Chen).
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spelling pubmed-106798642023-11-14 Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215) Zhao, Wensi Lei, Jun Ke, Shaobo Chen, Yuan Xiao, Jiping Tang, Ze Wang, Li Ren, Yiping Alnaggar, Mohammed Qiu, Hu Shi, Wei Yin, Lei Chen, Yongshun eClinicalMedicine Articles BACKGROUND: Immunotherapy has revolutionized the treatment of cancer. However, microsatellite stable (MSS) metastatic colorectal cancer (mCRC) shows a low response to PD-1 inhibitors. Antiangiogenic therapy can enhance anti-PD-1 efficacy, but it still cannot meet clinical needs. Increasing evidence supported a close relationship between gut microbiome and anti-PD-1 efficacy. This study aimed to explore the efficacy and safety of the combination of fecal microbiota transplantation (FMT) and tislelizumab and fruquintinib in refractory MSS mCRC. METHODS: In the phase II trial, MSS mCRC patients were administered FMT plus tislelizumab and fruquintinib as a third-line or above treatment. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), clinical benefit rate (CBR), safety and quality of life. Feces and peripheral blood were collected for exploratory biomarker analysis. This study is registered with Chictr.org.cn, identifier ChiCTR2100046768. FINDINGS: From May 10, 2021 to January 17, 2022, 20 patients were enrolled. Median follow-up was 13.7 months. Median PFS was 9.6 months (95% CI 4.1–15.1). Median OS was 13.7 months (95% CI 9.3–17.7). Median DoR was 8.1 months (95% CI 1.7–10.6). ORR was 20% (95% CI 5.7–43.7). DCR was 95% (95% CI 75.1–99.9). CBR was 60% (95% CI 36.1–80.9). Nineteen patients (95%) experienced at least one treatment-related adverse event (TRAE). Six patients (30%) had grade 3–4 TRAEs, with the most common being albuminuria (10%), urine occult blood (10%), fecal occult blood (10%), hypertension (5%), hyperglycemia (5%), liver dysfunction (5%), hand-foot skin reaction (5%), and hypothyroidism (5%). No treatment-related deaths occurred. Responders had a high-abundance of Proteobacteria and Lachnospiraceae family and a low-abundance of Actinobacteriota and Bifidobacterium. The treatment did not change the structure of peripheral blood TCR repertoire. However, the expanded TCRs exhibited the characteristics of antigen-driven responses in responders. INTERPRETATION: FMT plus tislelizumab and fruquintinib as third-line or above treatment showed improved survival and manageable safety in refractory MSS mCRC, suggesting a valuable new treatment option for this patient population. FUNDING: This study was supported by the 10.13039/501100001809National Natural Science Foundation of China (82102954 to Wensi Zhao) and the 10.13039/501100018570Special Project of Central Government for Local Science and Technology Development of Hubei Province (ZYYD2020000169 to Yongshun Chen). Elsevier 2023-11-14 /pmc/articles/PMC10679864/ /pubmed/38024475 http://dx.doi.org/10.1016/j.eclinm.2023.102315 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles
Zhao, Wensi
Lei, Jun
Ke, Shaobo
Chen, Yuan
Xiao, Jiping
Tang, Ze
Wang, Li
Ren, Yiping
Alnaggar, Mohammed
Qiu, Hu
Shi, Wei
Yin, Lei
Chen, Yongshun
Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215)
title Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215)
title_full Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215)
title_fullStr Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215)
title_full_unstemmed Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215)
title_short Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215)
title_sort fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase ii trial (renmin-215)
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10679864/
https://www.ncbi.nlm.nih.gov/pubmed/38024475
http://dx.doi.org/10.1016/j.eclinm.2023.102315
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