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Anlotinib Combined with Toripalimab as Second-Line Therapy for Advanced, Relapsed Gastric or Gastroesophageal Junction Carcinoma

Our study aimed to explore the efficacy and safety of anlotinib–toripalimab combination therapy as a second-line treatment for advanced relapsed gastric or gastroesophageal junction carcinoma (GC/GEJC). In this single arm, single-center extension clinical trial, patients with advanced relapsed GC/GE...

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Autores principales: Jiang, Man, Zhang, Chuantao, Hu, Yabin, Li, Tianjun, Yang, Guangjie, Wang, Guanqun, Zhu, Jingjuan, Shao, Changfeng, Hou, Helei, Zhou, Na, Liu, Kewei, Zhang, Xiaochun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632317/
https://www.ncbi.nlm.nih.gov/pubmed/35857405
http://dx.doi.org/10.1093/oncolo/oyac136
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author Jiang, Man
Zhang, Chuantao
Hu, Yabin
Li, Tianjun
Yang, Guangjie
Wang, Guanqun
Zhu, Jingjuan
Shao, Changfeng
Hou, Helei
Zhou, Na
Liu, Kewei
Zhang, Xiaochun
author_facet Jiang, Man
Zhang, Chuantao
Hu, Yabin
Li, Tianjun
Yang, Guangjie
Wang, Guanqun
Zhu, Jingjuan
Shao, Changfeng
Hou, Helei
Zhou, Na
Liu, Kewei
Zhang, Xiaochun
author_sort Jiang, Man
collection PubMed
description Our study aimed to explore the efficacy and safety of anlotinib–toripalimab combination therapy as a second-line treatment for advanced relapsed gastric or gastroesophageal junction carcinoma (GC/GEJC). In this single arm, single-center extension clinical trial, patients with advanced relapsed GC/GEJC received toripalimab (240 mg, intravenously over 60 minutes, once every 2 weeks) plus anlotinib (12 mg/day, orally, 2 weeks on and 1 week off, every 3 weeks) as second-line therapy. There were 29 patients who achieved partial response, and the ORR was 32.3% (95% CI, 26.6%-38.5%). Grade 3 treatment-related adverse events (TRAEs) were recorded in 7 participants (11.3%), all of which were manageable. The PFS and OS were 4.0 and 11.1 months, respectively. Patients with programmed death-ligand 1 (PD-L1) positive expression showed numerically longer OS than the negative ones although the difference was not significantly. The tumor mutational burden-high (TMB-H) group showed a significantly better OS (P = .05) than the TMB-Low (TMB-L) group. Next-generation sequencing (NGS) revealed that fibroblast growth factor receptor 2 (FGFR2) mutations positively correlated with target lesion reduction (odds ratio [OR] = 0.14; P = .02). The new regimen increased tumor-infiltration of CD8(+) T and CD3(+) T cells. Furthermore, a patient-derived organoid (PDO) study indicated that anlotinib could promote an immune-supportive tumor microenvironment. As conclusion, the anlotinib-toripalimab combination showed promising efficacy and favorable safety as a second-line treatment for advanced, relapsed GC/GEJC. The PD-L1 expression, TMB, and FGFR2 mutation are potential biomarkers for predicting the efficacy of this regimen (ClinicalTrials.gov registration number: NCT04713059).
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spelling pubmed-96323172022-11-04 Anlotinib Combined with Toripalimab as Second-Line Therapy for Advanced, Relapsed Gastric or Gastroesophageal Junction Carcinoma Jiang, Man Zhang, Chuantao Hu, Yabin Li, Tianjun Yang, Guangjie Wang, Guanqun Zhu, Jingjuan Shao, Changfeng Hou, Helei Zhou, Na Liu, Kewei Zhang, Xiaochun Oncologist Gastrointestinal Cancer Our study aimed to explore the efficacy and safety of anlotinib–toripalimab combination therapy as a second-line treatment for advanced relapsed gastric or gastroesophageal junction carcinoma (GC/GEJC). In this single arm, single-center extension clinical trial, patients with advanced relapsed GC/GEJC received toripalimab (240 mg, intravenously over 60 minutes, once every 2 weeks) plus anlotinib (12 mg/day, orally, 2 weeks on and 1 week off, every 3 weeks) as second-line therapy. There were 29 patients who achieved partial response, and the ORR was 32.3% (95% CI, 26.6%-38.5%). Grade 3 treatment-related adverse events (TRAEs) were recorded in 7 participants (11.3%), all of which were manageable. The PFS and OS were 4.0 and 11.1 months, respectively. Patients with programmed death-ligand 1 (PD-L1) positive expression showed numerically longer OS than the negative ones although the difference was not significantly. The tumor mutational burden-high (TMB-H) group showed a significantly better OS (P = .05) than the TMB-Low (TMB-L) group. Next-generation sequencing (NGS) revealed that fibroblast growth factor receptor 2 (FGFR2) mutations positively correlated with target lesion reduction (odds ratio [OR] = 0.14; P = .02). The new regimen increased tumor-infiltration of CD8(+) T and CD3(+) T cells. Furthermore, a patient-derived organoid (PDO) study indicated that anlotinib could promote an immune-supportive tumor microenvironment. As conclusion, the anlotinib-toripalimab combination showed promising efficacy and favorable safety as a second-line treatment for advanced, relapsed GC/GEJC. The PD-L1 expression, TMB, and FGFR2 mutation are potential biomarkers for predicting the efficacy of this regimen (ClinicalTrials.gov registration number: NCT04713059). Oxford University Press 2022-07-20 /pmc/articles/PMC9632317/ /pubmed/35857405 http://dx.doi.org/10.1093/oncolo/oyac136 Text en © The Author(s) 2022. Published by Oxford University Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gastrointestinal Cancer
Jiang, Man
Zhang, Chuantao
Hu, Yabin
Li, Tianjun
Yang, Guangjie
Wang, Guanqun
Zhu, Jingjuan
Shao, Changfeng
Hou, Helei
Zhou, Na
Liu, Kewei
Zhang, Xiaochun
Anlotinib Combined with Toripalimab as Second-Line Therapy for Advanced, Relapsed Gastric or Gastroesophageal Junction Carcinoma
title Anlotinib Combined with Toripalimab as Second-Line Therapy for Advanced, Relapsed Gastric or Gastroesophageal Junction Carcinoma
title_full Anlotinib Combined with Toripalimab as Second-Line Therapy for Advanced, Relapsed Gastric or Gastroesophageal Junction Carcinoma
title_fullStr Anlotinib Combined with Toripalimab as Second-Line Therapy for Advanced, Relapsed Gastric or Gastroesophageal Junction Carcinoma
title_full_unstemmed Anlotinib Combined with Toripalimab as Second-Line Therapy for Advanced, Relapsed Gastric or Gastroesophageal Junction Carcinoma
title_short Anlotinib Combined with Toripalimab as Second-Line Therapy for Advanced, Relapsed Gastric or Gastroesophageal Junction Carcinoma
title_sort anlotinib combined with toripalimab as second-line therapy for advanced, relapsed gastric or gastroesophageal junction carcinoma
topic Gastrointestinal Cancer
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632317/
https://www.ncbi.nlm.nih.gov/pubmed/35857405
http://dx.doi.org/10.1093/oncolo/oyac136
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