Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer
Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage gastric cancer, but their efficacy in the neoadjuvant/conversion setting is unclear. In this single-armed, ph...
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| Published in | Nature communications Vol. 14; no. 1; pp. 8 - 16 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
03.01.2023
Nature Publishing Group Nature Portfolio |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2041-1723 2041-1723 |
| DOI | 10.1038/s41467-022-35431-x |
Cover
| Abstract | Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage gastric cancer, but their efficacy in the neoadjuvant/conversion setting is unclear. In this single-armed, phase II, exploratory trial (NCT03878472), we evaluate the efficacy of a combination of ICI (camrelizumab), antiangiogenesis (apatinib), and chemotherapy (S-1 ± oxaliplatin) for neoadjuvant/conversion treatment of cT4a/bN+ gastric cancer. The primary endpoints are pathological responses and their potential biomarkers. Secondary endpoints include safety, objective response, progression-free survival, and overall survival. Complete and major pathological response rates are 15.8% and 26.3%. Pathological responses correlate significantly with microsatellite instability status, PD-L1 expression, and tumor mutational burden. In addition, multi-omics examination reveals several putative biomarkers for pathological responses, including
RREB1
and
SSPO
mutation, immune-related signatures, and a peripheral T cell expansion score. Multi-omics also demonstrates dynamic changes in dominant tumor subclones, immune microenvironments, and T cell receptor repertoires during neoadjuvant immunotherapy. The toxicity and post-surgery complications are limited. These data support further validation of ICI- and antiangiogenesis-based neoadjuvant/conversion therapy in large randomized trials and provide candidate biomarkers.
Immune checkpoint inhibitors and antiangiogenic agents have shown some activity in patients with late-stage gastric cancer. Here the authors report the results of a phase II trial of neoadjuvant anti-PD1 (camrelizumab), antiangiogenic agent (apatinib), and chemotherapy (S-1 ± Oxaliplatin) in stage T4a/bN + M0 gastric cancer patients. |
|---|---|
| AbstractList | Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage gastric cancer, but their efficacy in the neoadjuvant/conversion setting is unclear. In this single-armed, phase II, exploratory trial (NCT03878472), we evaluate the efficacy of a combination of ICI (camrelizumab), antiangiogenesis (apatinib), and chemotherapy (S-1 ± oxaliplatin) for neoadjuvant/conversion treatment of cT4a/bN+ gastric cancer. The primary endpoints are pathological responses and their potential biomarkers. Secondary endpoints include safety, objective response, progression-free survival, and overall survival. Complete and major pathological response rates are 15.8% and 26.3%. Pathological responses correlate significantly with microsatellite instability status, PD-L1 expression, and tumor mutational burden. In addition, multi-omics examination reveals several putative biomarkers for pathological responses, including RREB1 and SSPO mutation, immune-related signatures, and a peripheral T cell expansion score. Multi-omics also demonstrates dynamic changes in dominant tumor subclones, immune microenvironments, and T cell receptor repertoires during neoadjuvant immunotherapy. The toxicity and post-surgery complications are limited. These data support further validation of ICI- and antiangiogenesis-based neoadjuvant/conversion therapy in large randomized trials and provide candidate biomarkers.Immune checkpoint inhibitors and antiangiogenic agents have shown some activity in patients with late-stage gastric cancer. Here the authors report the results of a phase II trial of neoadjuvant anti-PD1 (camrelizumab), antiangiogenic agent (apatinib), and chemotherapy (S-1 ± Oxaliplatin) in stage T4a/bN + M0 gastric cancer patients. Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage gastric cancer, but their efficacy in the neoadjuvant/conversion setting is unclear. In this single-armed, phase II, exploratory trial (NCT03878472), we evaluate the efficacy of a combination of ICI (camrelizumab), antiangiogenesis (apatinib), and chemotherapy (S-1 ± oxaliplatin) for neoadjuvant/conversion treatment of cT4a/bN+ gastric cancer. The primary endpoints are pathological responses and their potential biomarkers. Secondary endpoints include safety, objective response, progression-free survival, and overall survival. Complete and major pathological response rates are 15.8% and 26.3%. Pathological responses correlate significantly with microsatellite instability status, PD-L1 expression, and tumor mutational burden. In addition, multi-omics examination reveals several putative biomarkers for pathological responses, including RREB1 and SSPO mutation, immune-related signatures, and a peripheral T cell expansion score. Multi-omics also demonstrates dynamic changes in dominant tumor subclones, immune microenvironments, and T cell receptor repertoires during neoadjuvant immunotherapy. The toxicity and post-surgery complications are limited. These data support further validation of ICI- and antiangiogenesis-based neoadjuvant/conversion therapy in large randomized trials and provide candidate biomarkers. Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage gastric cancer, but their efficacy in the neoadjuvant/conversion setting is unclear. In this single-armed, phase II, exploratory trial (NCT03878472), we evaluate the efficacy of a combination of ICI (camrelizumab), antiangiogenesis (apatinib), and chemotherapy (S-1 ± oxaliplatin) for neoadjuvant/conversion treatment of cT4a/bN+ gastric cancer. The primary endpoints are pathological responses and their potential biomarkers. Secondary endpoints include safety, objective response, progression-free survival, and overall survival. Complete and major pathological response rates are 15.8% and 26.3%. Pathological responses correlate significantly with microsatellite instability status, PD-L1 expression, and tumor mutational burden. In addition, multi-omics examination reveals several putative biomarkers for pathological responses, including RREB1 and SSPO mutation, immune-related signatures, and a peripheral T cell expansion score. Multi-omics also demonstrates dynamic changes in dominant tumor subclones, immune microenvironments, and T cell receptor repertoires during neoadjuvant immunotherapy. The toxicity and post-surgery complications are limited. These data support further validation of ICI- and antiangiogenesis-based neoadjuvant/conversion therapy in large randomized trials and provide candidate biomarkers. Immune checkpoint inhibitors and antiangiogenic agents have shown some activity in patients with late-stage gastric cancer. Here the authors report the results of a phase II trial of neoadjuvant anti-PD1 (camrelizumab), antiangiogenic agent (apatinib), and chemotherapy (S-1 ± Oxaliplatin) in stage T4a/bN + M0 gastric cancer patients. Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage gastric cancer, but their efficacy in the neoadjuvant/conversion setting is unclear. In this single-armed, phase II, exploratory trial (NCT03878472), we evaluate the efficacy of a combination of ICI (camrelizumab), antiangiogenesis (apatinib), and chemotherapy (S-1 ± oxaliplatin) for neoadjuvant/conversion treatment of cT4a/bN+ gastric cancer. The primary endpoints are pathological responses and their potential biomarkers. Secondary endpoints include safety, objective response, progression-free survival, and overall survival. Complete and major pathological response rates are 15.8% and 26.3%. Pathological responses correlate significantly with microsatellite instability status, PD-L1 expression, and tumor mutational burden. In addition, multi-omics examination reveals several putative biomarkers for pathological responses, including RREB1 and SSPO mutation, immune-related signatures, and a peripheral T cell expansion score. Multi-omics also demonstrates dynamic changes in dominant tumor subclones, immune microenvironments, and T cell receptor repertoires during neoadjuvant immunotherapy. The toxicity and post-surgery complications are limited. These data support further validation of ICI- and antiangiogenesis-based neoadjuvant/conversion therapy in large randomized trials and provide candidate biomarkers. Immune checkpoint inhibitors and antiangiogenic agents have shown some activity in patients with late-stage gastric cancer. Here the authors report the results of a phase II trial of neoadjuvant anti-PD1 (camrelizumab), antiangiogenic agent (apatinib), and chemotherapy (S-1 ± Oxaliplatin) in stage T4a/bN + M0 gastric cancer patients. Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage gastric cancer, but their efficacy in the neoadjuvant/conversion setting is unclear. In this single-armed, phase II, exploratory trial (NCT03878472), we evaluate the efficacy of a combination of ICI (camrelizumab), antiangiogenesis (apatinib), and chemotherapy (S-1 ± oxaliplatin) for neoadjuvant/conversion treatment of cT4a/bN+ gastric cancer. The primary endpoints are pathological responses and their potential biomarkers. Secondary endpoints include safety, objective response, progression-free survival, and overall survival. Complete and major pathological response rates are 15.8% and 26.3%. Pathological responses correlate significantly with microsatellite instability status, PD-L1 expression, and tumor mutational burden. In addition, multi-omics examination reveals several putative biomarkers for pathological responses, including RREB1 and SSPO mutation, immune-related signatures, and a peripheral T cell expansion score. Multi-omics also demonstrates dynamic changes in dominant tumor subclones, immune microenvironments, and T cell receptor repertoires during neoadjuvant immunotherapy. The toxicity and post-surgery complications are limited. These data support further validation of ICI- and antiangiogenesis-based neoadjuvant/conversion therapy in large randomized trials and provide candidate biomarkers.Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents have shown activity in late-stage gastric cancer, but their efficacy in the neoadjuvant/conversion setting is unclear. In this single-armed, phase II, exploratory trial (NCT03878472), we evaluate the efficacy of a combination of ICI (camrelizumab), antiangiogenesis (apatinib), and chemotherapy (S-1 ± oxaliplatin) for neoadjuvant/conversion treatment of cT4a/bN+ gastric cancer. The primary endpoints are pathological responses and their potential biomarkers. Secondary endpoints include safety, objective response, progression-free survival, and overall survival. Complete and major pathological response rates are 15.8% and 26.3%. Pathological responses correlate significantly with microsatellite instability status, PD-L1 expression, and tumor mutational burden. In addition, multi-omics examination reveals several putative biomarkers for pathological responses, including RREB1 and SSPO mutation, immune-related signatures, and a peripheral T cell expansion score. Multi-omics also demonstrates dynamic changes in dominant tumor subclones, immune microenvironments, and T cell receptor repertoires during neoadjuvant immunotherapy. The toxicity and post-surgery complications are limited. These data support further validation of ICI- and antiangiogenesis-based neoadjuvant/conversion therapy in large randomized trials and provide candidate biomarkers. |
| ArticleNumber | 8 |
| Author | Li, Song Wang, Jian Shi, Duanbo Yu, Dexin Wei, Meng Liu, Zhimin Wang, Jiaqian Xie, Fei Dai, Xin Gao, Peng Xu, Qian Sheng, Lei Luo, Haitao Zhao, Zhikun Zhou, Wenhao Lv, Weiwei Yu, Wenbin Zhang, Xue Li, Jisheng Chen, Cheng Liu, Lian Huang, Miao Huang, Kai |
| Author_xml | – sequence: 1 givenname: Song orcidid: 0000-0002-5023-9111 surname: Li fullname: Li, Song organization: Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University – sequence: 2 givenname: Wenbin surname: Yu fullname: Yu, Wenbin organization: Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University – sequence: 3 givenname: Fei surname: Xie fullname: Xie, Fei organization: Department of Pharmacy, Qilu Hospital, Cheeloo College of Medicine, Shandong University – sequence: 4 givenname: Haitao surname: Luo fullname: Luo, Haitao organization: Shenzhen Yucebio Technology Co., Ltd., Shenzhen – sequence: 5 givenname: Zhimin surname: Liu fullname: Liu, Zhimin organization: Department of General Surgery, Zibo Municipal Central Hospital, Binzhou Medical College – sequence: 6 givenname: Weiwei surname: Lv fullname: Lv, Weiwei organization: Department of Radiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University – sequence: 7 givenname: Duanbo surname: Shi fullname: Shi, Duanbo organization: Department of Pathology, Qilu Hospital, Cheeloo College of Medicine, Shandong University – sequence: 8 givenname: Dexin orcidid: 0000-0001-7462-3153 surname: Yu fullname: Yu, Dexin organization: Department of Radiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University – sequence: 9 givenname: Peng orcidid: 0000-0002-4721-0887 surname: Gao fullname: Gao, Peng organization: Department of Pathology, Qilu Hospital, Cheeloo College of Medicine, Shandong University – sequence: 10 givenname: Cheng surname: Chen fullname: Chen, Cheng organization: Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University – sequence: 11 givenname: Meng surname: Wei fullname: Wei, Meng organization: Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University – sequence: 12 givenname: Wenhao surname: Zhou fullname: Zhou, Wenhao organization: Shenzhen Yucebio Technology Co., Ltd., Shenzhen – sequence: 13 givenname: Jiaqian surname: Wang fullname: Wang, Jiaqian organization: Shenzhen Yucebio Technology Co., Ltd., Shenzhen – sequence: 14 givenname: Zhikun surname: Zhao fullname: Zhao, Zhikun organization: Shenzhen Yucebio Technology Co., Ltd., Shenzhen – sequence: 15 givenname: Xin surname: Dai fullname: Dai, Xin organization: Department of Medical Oncology, Shandong Provincial Hospital of Traditional Chinese Medicine – sequence: 16 givenname: Qian surname: Xu fullname: Xu, Qian organization: Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University – sequence: 17 givenname: Xue surname: Zhang fullname: Zhang, Xue organization: Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University – sequence: 18 givenname: Miao surname: Huang fullname: Huang, Miao organization: Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University – sequence: 19 givenname: Kai surname: Huang fullname: Huang, Kai organization: Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University – sequence: 20 givenname: Jian surname: Wang fullname: Wang, Jian organization: Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University – sequence: 21 givenname: Jisheng surname: Li fullname: Li, Jisheng organization: Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University – sequence: 22 givenname: Lei surname: Sheng fullname: Sheng, Lei organization: Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University – sequence: 23 givenname: Lian orcidid: 0000-0001-5868-4482 surname: Liu fullname: Liu, Lian email: lianliu@sdu.edu.cn organization: Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36596787$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | The Author(s) 2023 2023. The Author(s). The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
| Copyright_xml | – notice: The Author(s) 2023 – notice: 2023. The Author(s). – notice: The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
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| DOI | 10.1038/s41467-022-35431-x |
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| Snippet | Despite neoadjuvant/conversion chemotherapy, the prognosis of cT4a/bN+ gastric cancer is poor. Immune checkpoint inhibitors (ICIs) and antiangiogenic agents... Immune checkpoint inhibitors and antiangiogenic agents have shown some activity in patients with late-stage gastric cancer. Here the authors report the results... |
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| SubjectTerms | 13/1 49/23 49/39 631/67/1504/1829 692/4028/67/1059/2325 692/4028/67/1504/1829 82/51 Antiangiogenic agents Antiangiogenics Biomarkers Cancer Cancer therapies Chemotherapy Clinical trials Conversion Effectiveness Gastric cancer Humanities and Social Sciences Humans Immune checkpoint inhibitors Immune Checkpoint Inhibitors - therapeutic use Immunotherapy Inhibitors Lymphocytes Lymphocytes T Medical prognosis Microenvironments Microsatellite instability multidisciplinary Mutation Neoadjuvant Therapy Oxaliplatin Patients PD-1 protein PD-L1 protein Progression-Free Survival Science Science (multidisciplinary) Stomach Neoplasms - drug therapy Stomach Neoplasms - genetics Survival T cell receptors Toxicity Tumor Microenvironment Tumors |
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| Title | Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer |
| URI | https://link.springer.com/article/10.1038/s41467-022-35431-x https://www.ncbi.nlm.nih.gov/pubmed/36596787 https://www.proquest.com/docview/2760393135 https://www.proquest.com/docview/2760817842 https://pubmed.ncbi.nlm.nih.gov/PMC9810618 https://doaj.org/article/a4e190d3b92f4b949cc25d4b09eb4a42 |
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