Intensive cycles of neoadjuvant camrelizumab combined with chemotherapy in locally advanced esophageal squamous cell carcinoma: a single-arm, phase II trial
Abstract Background Two cycles of neoadjuvant PD-1 blockade plus chemotherapy induced favorable pathological response and tolerant toxicity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 25% of patients relapsed within 1 year after surgery, indica...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-06-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04273-6 |
| _version_ | 1797795520959217664 |
|---|---|
| author | Guozhen Yang Xiaodong Su Yuanheng Huang Guangyu Luo Zhiqiang Wang Peiqiang Cai Yating Zheng Ting Bei Mengli Huang Yuezong Bai Haoqiang He Jin Xiang Muyan Cai Jiudi Zhong Qiyu Guo Xu Zhang |
| author_facet | Guozhen Yang Xiaodong Su Yuanheng Huang Guangyu Luo Zhiqiang Wang Peiqiang Cai Yating Zheng Ting Bei Mengli Huang Yuezong Bai Haoqiang He Jin Xiang Muyan Cai Jiudi Zhong Qiyu Guo Xu Zhang |
| author_sort | Guozhen Yang |
| collection | DOAJ |
| description | Abstract Background Two cycles of neoadjuvant PD-1 blockade plus chemotherapy induced favorable pathological response and tolerant toxicity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 25% of patients relapsed within 1 year after surgery, indicating that a short course of treatment may not be sufficient. Therefore, exploring the effects of intensive treatment is needed for optimal clinical outcomes. Methods Locally advanced ESCC patients were administered three cycles of camrelizumab plus nab-paclitaxel and capecitabine, followed by thoracoscopic esophagectomy. The primary endpoint was pathologic response. Secondary endpoints included safety, feasibility, radiologic response, survival outcomes, and immunologic/genomic correlates of efficacy. Results Forty-seven patients were enrolled in the study. Forty-two patients received surgery, and R0 resection was achieved in all cases. The complete and major pathological response rates were 33.3% and 64.3%, respectively, and the objective response rate was 80.0%. Three cycles of treatment significantly improved T down-staging compared to two cycles (P = 0.03). The most common treatment-related adverse events were grades 1–2, and no surgical delay was reported. With a median follow-up of 24.3 months, the 1-year disease-free survival and overall survival rates were both 97.6%, and the 2-year disease-free survival and overall survival rates were 92.3% and 97.6%, respectively. Three patients experienced disease recurrence or metastasis ranging from 12.5 to 25.8 months after surgery, and one patient died 6 months after surgery due to cardiovascular disease. Neither programmed death-ligand 1 expression nor tumor mutational burden was associated with pathological response. An increased infiltration of CD56 dim natural killer cells in the pretreatment tumor was correlated with better pathological response in the primary tumor. Conclusions It seems probable that intensive cycles of neoadjuvant camrelizumab plus nab-paclitaxel and capecitabine increased tumor regression and improved survival outcomes. Randomized controlled trials with larger sample sizes and longer follow-up periods are needed to validate these findings. Trial registration Chinese Clinical Trial Registry, ChiCTR2000029807, Registered February 14, 2020, https://www.chictr.org.cn/showproj.aspx?proj=49459 . |
| first_indexed | 2024-03-13T03:19:14Z |
| format | Article |
| id | doaj.art-833b3f4cc1c84667bf397de83432f82f |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-13T03:19:14Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-833b3f4cc1c84667bf397de83432f82f2023-06-25T11:26:10ZengBMCJournal of Translational Medicine1479-58762023-06-0121111110.1186/s12967-023-04273-6Intensive cycles of neoadjuvant camrelizumab combined with chemotherapy in locally advanced esophageal squamous cell carcinoma: a single-arm, phase II trialGuozhen Yang0Xiaodong Su1Yuanheng Huang2Guangyu Luo3Zhiqiang Wang4Peiqiang Cai5Yating Zheng6Ting Bei7Mengli Huang8Yuezong Bai9Haoqiang He10Jin Xiang11Muyan Cai12Jiudi Zhong13Qiyu Guo14Xu Zhang15Department of Thoracic Oncology, Sun Yat-Sen University Cancer CenterDepartment of Thoracic Oncology, Sun Yat-Sen University Cancer CenterDepartment of Thoracic Oncology, Sun Yat-Sen University Cancer CenterState Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer MedicineState Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer MedicineState Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer MedicineMedical Affairs, 3D Medicines, IncMedical Affairs, 3D Medicines, IncMedical Affairs, 3D Medicines, IncMedical Affairs, 3D Medicines, IncState Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer MedicineState Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer MedicineState Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer MedicineDepartment of Thoracic Oncology, Sun Yat-Sen University Cancer CenterDepartment of Thoracic Oncology, Sun Yat-Sen University Cancer CenterDepartment of Thoracic Oncology, Sun Yat-Sen University Cancer CenterAbstract Background Two cycles of neoadjuvant PD-1 blockade plus chemotherapy induced favorable pathological response and tolerant toxicity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 25% of patients relapsed within 1 year after surgery, indicating that a short course of treatment may not be sufficient. Therefore, exploring the effects of intensive treatment is needed for optimal clinical outcomes. Methods Locally advanced ESCC patients were administered three cycles of camrelizumab plus nab-paclitaxel and capecitabine, followed by thoracoscopic esophagectomy. The primary endpoint was pathologic response. Secondary endpoints included safety, feasibility, radiologic response, survival outcomes, and immunologic/genomic correlates of efficacy. Results Forty-seven patients were enrolled in the study. Forty-two patients received surgery, and R0 resection was achieved in all cases. The complete and major pathological response rates were 33.3% and 64.3%, respectively, and the objective response rate was 80.0%. Three cycles of treatment significantly improved T down-staging compared to two cycles (P = 0.03). The most common treatment-related adverse events were grades 1–2, and no surgical delay was reported. With a median follow-up of 24.3 months, the 1-year disease-free survival and overall survival rates were both 97.6%, and the 2-year disease-free survival and overall survival rates were 92.3% and 97.6%, respectively. Three patients experienced disease recurrence or metastasis ranging from 12.5 to 25.8 months after surgery, and one patient died 6 months after surgery due to cardiovascular disease. Neither programmed death-ligand 1 expression nor tumor mutational burden was associated with pathological response. An increased infiltration of CD56 dim natural killer cells in the pretreatment tumor was correlated with better pathological response in the primary tumor. Conclusions It seems probable that intensive cycles of neoadjuvant camrelizumab plus nab-paclitaxel and capecitabine increased tumor regression and improved survival outcomes. Randomized controlled trials with larger sample sizes and longer follow-up periods are needed to validate these findings. Trial registration Chinese Clinical Trial Registry, ChiCTR2000029807, Registered February 14, 2020, https://www.chictr.org.cn/showproj.aspx?proj=49459 .https://doi.org/10.1186/s12967-023-04273-6NeoadjuvantImmunotherapyChemotherapyESCC |
| spellingShingle | Guozhen Yang Xiaodong Su Yuanheng Huang Guangyu Luo Zhiqiang Wang Peiqiang Cai Yating Zheng Ting Bei Mengli Huang Yuezong Bai Haoqiang He Jin Xiang Muyan Cai Jiudi Zhong Qiyu Guo Xu Zhang Intensive cycles of neoadjuvant camrelizumab combined with chemotherapy in locally advanced esophageal squamous cell carcinoma: a single-arm, phase II trial Journal of Translational Medicine Neoadjuvant Immunotherapy Chemotherapy ESCC |
| title | Intensive cycles of neoadjuvant camrelizumab combined with chemotherapy in locally advanced esophageal squamous cell carcinoma: a single-arm, phase II trial |
| title_full | Intensive cycles of neoadjuvant camrelizumab combined with chemotherapy in locally advanced esophageal squamous cell carcinoma: a single-arm, phase II trial |
| title_fullStr | Intensive cycles of neoadjuvant camrelizumab combined with chemotherapy in locally advanced esophageal squamous cell carcinoma: a single-arm, phase II trial |
| title_full_unstemmed | Intensive cycles of neoadjuvant camrelizumab combined with chemotherapy in locally advanced esophageal squamous cell carcinoma: a single-arm, phase II trial |
| title_short | Intensive cycles of neoadjuvant camrelizumab combined with chemotherapy in locally advanced esophageal squamous cell carcinoma: a single-arm, phase II trial |
| title_sort | intensive cycles of neoadjuvant camrelizumab combined with chemotherapy in locally advanced esophageal squamous cell carcinoma a single arm phase ii trial |
| topic | Neoadjuvant Immunotherapy Chemotherapy ESCC |
| url | https://doi.org/10.1186/s12967-023-04273-6 |
| work_keys_str_mv | AT guozhenyang intensivecyclesofneoadjuvantcamrelizumabcombinedwithchemotherapyinlocallyadvancedesophagealsquamouscellcarcinomaasinglearmphaseiitrial AT xiaodongsu intensivecyclesofneoadjuvantcamrelizumabcombinedwithchemotherapyinlocallyadvancedesophagealsquamouscellcarcinomaasinglearmphaseiitrial AT yuanhenghuang intensivecyclesofneoadjuvantcamrelizumabcombinedwithchemotherapyinlocallyadvancedesophagealsquamouscellcarcinomaasinglearmphaseiitrial AT guangyuluo intensivecyclesofneoadjuvantcamrelizumabcombinedwithchemotherapyinlocallyadvancedesophagealsquamouscellcarcinomaasinglearmphaseiitrial AT zhiqiangwang intensivecyclesofneoadjuvantcamrelizumabcombinedwithchemotherapyinlocallyadvancedesophagealsquamouscellcarcinomaasinglearmphaseiitrial AT peiqiangcai intensivecyclesofneoadjuvantcamrelizumabcombinedwithchemotherapyinlocallyadvancedesophagealsquamouscellcarcinomaasinglearmphaseiitrial AT yatingzheng intensivecyclesofneoadjuvantcamrelizumabcombinedwithchemotherapyinlocallyadvancedesophagealsquamouscellcarcinomaasinglearmphaseiitrial AT tingbei intensivecyclesofneoadjuvantcamrelizumabcombinedwithchemotherapyinlocallyadvancedesophagealsquamouscellcarcinomaasinglearmphaseiitrial AT menglihuang intensivecyclesofneoadjuvantcamrelizumabcombinedwithchemotherapyinlocallyadvancedesophagealsquamouscellcarcinomaasinglearmphaseiitrial AT yuezongbai intensivecyclesofneoadjuvantcamrelizumabcombinedwithchemotherapyinlocallyadvancedesophagealsquamouscellcarcinomaasinglearmphaseiitrial AT haoqianghe intensivecyclesofneoadjuvantcamrelizumabcombinedwithchemotherapyinlocallyadvancedesophagealsquamouscellcarcinomaasinglearmphaseiitrial AT jinxiang intensivecyclesofneoadjuvantcamrelizumabcombinedwithchemotherapyinlocallyadvancedesophagealsquamouscellcarcinomaasinglearmphaseiitrial AT muyancai intensivecyclesofneoadjuvantcamrelizumabcombinedwithchemotherapyinlocallyadvancedesophagealsquamouscellcarcinomaasinglearmphaseiitrial AT jiudizhong intensivecyclesofneoadjuvantcamrelizumabcombinedwithchemotherapyinlocallyadvancedesophagealsquamouscellcarcinomaasinglearmphaseiitrial AT qiyuguo intensivecyclesofneoadjuvantcamrelizumabcombinedwithchemotherapyinlocallyadvancedesophagealsquamouscellcarcinomaasinglearmphaseiitrial AT xuzhang intensivecyclesofneoadjuvantcamrelizumabcombinedwithchemotherapyinlocallyadvancedesophagealsquamouscellcarcinomaasinglearmphaseiitrial |