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Neoadjuvant therapy with camrelizumab plus gemcitabine and cisplatin for patients with muscle‐invasive bladder cancer: A multi‐center, single‐arm, phase 2 study

BACKGROUND: Neoadjuvant chemotherapy followed by radical cystectomy (RC) is the standard of care for patients with muscle‐invasive bladder cancer (MIBC). However, treatment outcomes are suboptimal. Camrelizumab, a PD‐1 blockade, has shown benefits in several tumors. This study aimed to investigate t...

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Autores principales: Han, Sujun, Ji, Zhigang, Jiang, Junhui, Fan, Xinrong, Ma, Qi, Hu, Linjun, Zhang, Wen, Ping, Hao, Wang, Jiansong, Xu, Wanhai, Shi, Benkang, Wang, Wei, Wang, Haifeng, Wang, Honglei, Chen, Shouzhen, Hu, Hailong, Guo, Jianming, Zhang, Shen, Jiang, Shuai, Zhou, Quan, Xing, Nianzeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278497/
https://www.ncbi.nlm.nih.gov/pubmed/37021811
http://dx.doi.org/10.1002/cam4.5900
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author Han, Sujun
Ji, Zhigang
Jiang, Junhui
Fan, Xinrong
Ma, Qi
Hu, Linjun
Zhang, Wen
Ping, Hao
Wang, Jiansong
Xu, Wanhai
Shi, Benkang
Wang, Wei
Wang, Haifeng
Wang, Honglei
Chen, Shouzhen
Hu, Hailong
Guo, Jianming
Zhang, Shen
Jiang, Shuai
Zhou, Quan
Xing, Nianzeng
author_facet Han, Sujun
Ji, Zhigang
Jiang, Junhui
Fan, Xinrong
Ma, Qi
Hu, Linjun
Zhang, Wen
Ping, Hao
Wang, Jiansong
Xu, Wanhai
Shi, Benkang
Wang, Wei
Wang, Haifeng
Wang, Honglei
Chen, Shouzhen
Hu, Hailong
Guo, Jianming
Zhang, Shen
Jiang, Shuai
Zhou, Quan
Xing, Nianzeng
author_sort Han, Sujun
collection PubMed
description BACKGROUND: Neoadjuvant chemotherapy followed by radical cystectomy (RC) is the standard of care for patients with muscle‐invasive bladder cancer (MIBC). However, treatment outcomes are suboptimal. Camrelizumab, a PD‐1 blockade, has shown benefits in several tumors. This study aimed to investigate the efficacy and safety of neoadjuvant camrelizumab in combination with gemcitabine plus cisplatin (GC) followed by RC for MIBC patients. METHODS: This was a multi‐center, single‐arm study that enrolled MIBC patients with a clinical stage of T2‐4aN0‐1M0, and scheduled for RC. Patients received three 21‐day cycles of camrelizumab 200 mg on day 1, gemcitabine 1000 mg/m(2) on day 1 and 8, and cisplatin 70 mg/m(2) on day 2, followed by RC. The primary endpoint was pathologic complete response (pCR, pT0N0). RESULTS: From May 2020 to July 2021, 43 patients were enrolled and received study medications at nine centers in China. Three of them were deemed ineligible and excluded from efficacy analysis but included in safety analysis. In total 10 patients were unevaluable as they declined RC (two due to adverse events [AEs] and eight due to patient's willingness). Among 30 evaluable patients, 13 patients (43.3%) achieved pCR, and 16 patients (53.3%) achieved pathologic downstaging. No AEs leading to death were observed. The most common AEs were anemia (69.8%), decreased white blood cell count (65.1%), and nausea (65.1%). Immune‐related AEs were all grade 1 or 2. Pathologic response was not correlated with PD‐L1 expression status or tumor mutation burden. Individual genes as a biomarker for pathologic response were not identified. CONCLUSIONS: Neoadjuvant treatment with camrelizumab and GC regimen demonstrated preliminary anti‐tumor activity for MIBC patients with manageable safety profiles. The study met its primary endpoint, and the following randomized trial is ongoing.
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spelling pubmed-102784972023-06-20 Neoadjuvant therapy with camrelizumab plus gemcitabine and cisplatin for patients with muscle‐invasive bladder cancer: A multi‐center, single‐arm, phase 2 study Han, Sujun Ji, Zhigang Jiang, Junhui Fan, Xinrong Ma, Qi Hu, Linjun Zhang, Wen Ping, Hao Wang, Jiansong Xu, Wanhai Shi, Benkang Wang, Wei Wang, Haifeng Wang, Honglei Chen, Shouzhen Hu, Hailong Guo, Jianming Zhang, Shen Jiang, Shuai Zhou, Quan Xing, Nianzeng Cancer Med RESEARCH ARTICLES BACKGROUND: Neoadjuvant chemotherapy followed by radical cystectomy (RC) is the standard of care for patients with muscle‐invasive bladder cancer (MIBC). However, treatment outcomes are suboptimal. Camrelizumab, a PD‐1 blockade, has shown benefits in several tumors. This study aimed to investigate the efficacy and safety of neoadjuvant camrelizumab in combination with gemcitabine plus cisplatin (GC) followed by RC for MIBC patients. METHODS: This was a multi‐center, single‐arm study that enrolled MIBC patients with a clinical stage of T2‐4aN0‐1M0, and scheduled for RC. Patients received three 21‐day cycles of camrelizumab 200 mg on day 1, gemcitabine 1000 mg/m(2) on day 1 and 8, and cisplatin 70 mg/m(2) on day 2, followed by RC. The primary endpoint was pathologic complete response (pCR, pT0N0). RESULTS: From May 2020 to July 2021, 43 patients were enrolled and received study medications at nine centers in China. Three of them were deemed ineligible and excluded from efficacy analysis but included in safety analysis. In total 10 patients were unevaluable as they declined RC (two due to adverse events [AEs] and eight due to patient's willingness). Among 30 evaluable patients, 13 patients (43.3%) achieved pCR, and 16 patients (53.3%) achieved pathologic downstaging. No AEs leading to death were observed. The most common AEs were anemia (69.8%), decreased white blood cell count (65.1%), and nausea (65.1%). Immune‐related AEs were all grade 1 or 2. Pathologic response was not correlated with PD‐L1 expression status or tumor mutation burden. Individual genes as a biomarker for pathologic response were not identified. CONCLUSIONS: Neoadjuvant treatment with camrelizumab and GC regimen demonstrated preliminary anti‐tumor activity for MIBC patients with manageable safety profiles. The study met its primary endpoint, and the following randomized trial is ongoing. John Wiley and Sons Inc. 2023-04-06 /pmc/articles/PMC10278497/ /pubmed/37021811 http://dx.doi.org/10.1002/cam4.5900 Text en © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle RESEARCH ARTICLES
Han, Sujun
Ji, Zhigang
Jiang, Junhui
Fan, Xinrong
Ma, Qi
Hu, Linjun
Zhang, Wen
Ping, Hao
Wang, Jiansong
Xu, Wanhai
Shi, Benkang
Wang, Wei
Wang, Haifeng
Wang, Honglei
Chen, Shouzhen
Hu, Hailong
Guo, Jianming
Zhang, Shen
Jiang, Shuai
Zhou, Quan
Xing, Nianzeng
Neoadjuvant therapy with camrelizumab plus gemcitabine and cisplatin for patients with muscle‐invasive bladder cancer: A multi‐center, single‐arm, phase 2 study
title Neoadjuvant therapy with camrelizumab plus gemcitabine and cisplatin for patients with muscle‐invasive bladder cancer: A multi‐center, single‐arm, phase 2 study
title_full Neoadjuvant therapy with camrelizumab plus gemcitabine and cisplatin for patients with muscle‐invasive bladder cancer: A multi‐center, single‐arm, phase 2 study
title_fullStr Neoadjuvant therapy with camrelizumab plus gemcitabine and cisplatin for patients with muscle‐invasive bladder cancer: A multi‐center, single‐arm, phase 2 study
title_full_unstemmed Neoadjuvant therapy with camrelizumab plus gemcitabine and cisplatin for patients with muscle‐invasive bladder cancer: A multi‐center, single‐arm, phase 2 study
title_short Neoadjuvant therapy with camrelizumab plus gemcitabine and cisplatin for patients with muscle‐invasive bladder cancer: A multi‐center, single‐arm, phase 2 study
title_sort neoadjuvant therapy with camrelizumab plus gemcitabine and cisplatin for patients with muscle‐invasive bladder cancer: a multi‐center, single‐arm, phase 2 study
topic RESEARCH ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278497/
https://www.ncbi.nlm.nih.gov/pubmed/37021811
http://dx.doi.org/10.1002/cam4.5900
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