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The Safety and Efficacy of Camrelizumab and Its Combination With Apatinib in Various Solid Cancers

Background: Camrelizumab (SHR1210) is a high-affinity, humanized immunoglobulin programmed cell death 1 (PD-1) monoclonal antibody. It was developed by Jiangsu Hengrui Medicine Co. Ltd. and has been approved for relapsed or refractory classical Hodgkin lymphoma patients and hepatocellular carcinoma...

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Autores principales: Wang, Kunlun, Li, Bingxu, Li, Mengxi, Li, Shenglei, Yang, Hui, Yuan, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609870/
http://dx.doi.org/10.3389/fphar.2020.568477
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author Wang, Kunlun
Li, Bingxu
Li, Mengxi
Li, Shenglei
Yang, Hui
Yuan, Ling
author_facet Wang, Kunlun
Li, Bingxu
Li, Mengxi
Li, Shenglei
Yang, Hui
Yuan, Ling
author_sort Wang, Kunlun
collection PubMed
description Background: Camrelizumab (SHR1210) is a high-affinity, humanized immunoglobulin programmed cell death 1 (PD-1) monoclonal antibody. It was developed by Jiangsu Hengrui Medicine Co. Ltd. and has been approved for relapsed or refractory classical Hodgkin lymphoma patients and hepatocellular carcinoma patients in China. Apatinib is an orally administered vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor and has been approved for advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma in China. Camrelizumab alone and its combination with apatinib have been used in the treatment of various solid cancers. Methods: We searched Embase, PubMed, and other databases with the keyword “camrelizumab” or “SHR1210,” and evaluated the safety and efficacy data of the involved studies. Adverse events (AEs) mentioned in at least two studies were summarized, including any grade and grade ≥3 treatment-related AEs. Meanwhile, efficacy data were collected, such as overall response rate (ORR), disease control rate (DCR), duration of response, 6-month progression-free survival (PFS) rate, median PFS time, 12-month overall survival rate, and median overall survival time. Results: The major AEs of camrelizumab alone were reactive cutaneous capillary endothelial proliferation, fatigue, aspartate aminotransferase increase, proteinuria, pruritus, and alanine transaminase increase. The ORR and DCR were 20.2% (95% CI: 15.1–26.6%, p = 0.000, I(2) = 70.360) and 45.8% (95% CI: 39.0–52.7%, p = 0.256, I(2) = 58.661), respectively. In the three studies of combination therapy, two studies were combined with apatinib and one combined with chemotherapy. For these studies, common AEs were hypertension, platelet count decrease, nausea, proteinuria, aspartate aminotransferase increase, and white blood cell count decrease. The pooled ORR, DCR, and 6-month PFS rate were 41.8% (95% CI: 29.7–54.9%, p = 0.220, I(2) = 86.265), 82.4% (95% CI: 75.9–87.4%, p = 0.000, I(2) = 55.207), and 56.2% (95% CI: 35.8–74.6%, p = 0.559, I(2) = 79.739), respectively. Conclusion: Camrelizumab and its combination are tolerable and appear to be efficient in treating numerous solid cancers. The combination therapy appears to have better efficacy with durable toxicity. However, these remain to be shown in future studies. Besides, baseline lactate dehydrogenase, programmed cell death ligand 1 (PD-L1) expression, tumor mutation burden, and the incidence of reactive cutaneous capillary endothelial proliferation may be efficacy predictors and need to be clarified in further studies.
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spelling pubmed-76098702020-11-13 The Safety and Efficacy of Camrelizumab and Its Combination With Apatinib in Various Solid Cancers Wang, Kunlun Li, Bingxu Li, Mengxi Li, Shenglei Yang, Hui Yuan, Ling Front Pharmacol Pharmacology Background: Camrelizumab (SHR1210) is a high-affinity, humanized immunoglobulin programmed cell death 1 (PD-1) monoclonal antibody. It was developed by Jiangsu Hengrui Medicine Co. Ltd. and has been approved for relapsed or refractory classical Hodgkin lymphoma patients and hepatocellular carcinoma patients in China. Apatinib is an orally administered vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor and has been approved for advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma in China. Camrelizumab alone and its combination with apatinib have been used in the treatment of various solid cancers. Methods: We searched Embase, PubMed, and other databases with the keyword “camrelizumab” or “SHR1210,” and evaluated the safety and efficacy data of the involved studies. Adverse events (AEs) mentioned in at least two studies were summarized, including any grade and grade ≥3 treatment-related AEs. Meanwhile, efficacy data were collected, such as overall response rate (ORR), disease control rate (DCR), duration of response, 6-month progression-free survival (PFS) rate, median PFS time, 12-month overall survival rate, and median overall survival time. Results: The major AEs of camrelizumab alone were reactive cutaneous capillary endothelial proliferation, fatigue, aspartate aminotransferase increase, proteinuria, pruritus, and alanine transaminase increase. The ORR and DCR were 20.2% (95% CI: 15.1–26.6%, p = 0.000, I(2) = 70.360) and 45.8% (95% CI: 39.0–52.7%, p = 0.256, I(2) = 58.661), respectively. In the three studies of combination therapy, two studies were combined with apatinib and one combined with chemotherapy. For these studies, common AEs were hypertension, platelet count decrease, nausea, proteinuria, aspartate aminotransferase increase, and white blood cell count decrease. The pooled ORR, DCR, and 6-month PFS rate were 41.8% (95% CI: 29.7–54.9%, p = 0.220, I(2) = 86.265), 82.4% (95% CI: 75.9–87.4%, p = 0.000, I(2) = 55.207), and 56.2% (95% CI: 35.8–74.6%, p = 0.559, I(2) = 79.739), respectively. Conclusion: Camrelizumab and its combination are tolerable and appear to be efficient in treating numerous solid cancers. The combination therapy appears to have better efficacy with durable toxicity. However, these remain to be shown in future studies. Besides, baseline lactate dehydrogenase, programmed cell death ligand 1 (PD-L1) expression, tumor mutation burden, and the incidence of reactive cutaneous capillary endothelial proliferation may be efficacy predictors and need to be clarified in further studies. Frontiers Media S.A. 2020-10-21 /pmc/articles/PMC7609870/ http://dx.doi.org/10.3389/fphar.2020.568477 Text en Copyright © 2020 Wang, Li, Li, Li, Yang and Yuan http://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 Pharmacology
Wang, Kunlun
Li, Bingxu
Li, Mengxi
Li, Shenglei
Yang, Hui
Yuan, Ling
The Safety and Efficacy of Camrelizumab and Its Combination With Apatinib in Various Solid Cancers
title The Safety and Efficacy of Camrelizumab and Its Combination With Apatinib in Various Solid Cancers
title_full The Safety and Efficacy of Camrelizumab and Its Combination With Apatinib in Various Solid Cancers
title_fullStr The Safety and Efficacy of Camrelizumab and Its Combination With Apatinib in Various Solid Cancers
title_full_unstemmed The Safety and Efficacy of Camrelizumab and Its Combination With Apatinib in Various Solid Cancers
title_short The Safety and Efficacy of Camrelizumab and Its Combination With Apatinib in Various Solid Cancers
title_sort safety and efficacy of camrelizumab and its combination with apatinib in various solid cancers
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609870/
http://dx.doi.org/10.3389/fphar.2020.568477
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