Preoperative pembrolizumab combined with chemoradiotherapy for esophageal squamous cell carcinoma: Trial designCentral MessagePerspective
Objective: The safety and feasibility of preoperative pembrolizumab combined with chemoradiotherapy (PPCT) for resectable esophageal squamous cell carcinoma have been confirmed by the prior Preoperative Anti-PD-1 Antibody combined with Chemoradiotherapy for Locally Advanced Squmous Cell Carcinoma of...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-03-01
|
| Series: | JTCVS Open |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666273621004228 |
| _version_ | 1828806279665025024 |
|---|---|
| author | Yuyan Zheng, MD Chengqiang Li, MD, PhD Bentong Yu, MD Shengguang Zhao, MD Jian Li, MD, PhD Xiaoyan Chen, MD Hecheng Li, MD, PhD, FACS |
| author_facet | Yuyan Zheng, MD Chengqiang Li, MD, PhD Bentong Yu, MD Shengguang Zhao, MD Jian Li, MD, PhD Xiaoyan Chen, MD Hecheng Li, MD, PhD, FACS |
| author_sort | Yuyan Zheng, MD |
| collection | DOAJ |
| description | Objective: The safety and feasibility of preoperative pembrolizumab combined with chemoradiotherapy (PPCT) for resectable esophageal squamous cell carcinoma have been confirmed by the prior Preoperative Anti-PD-1 Antibody combined with Chemoradiotherapy for Locally Advanced Squmous Cell Carcinoma of Esophageus (PALACE)-1 trial. Potential therapeutic benefit was also observed with a pathologic complete response rate of 55.6% after PPCT. We will conduct the multicenter single-arm PALACE-2 study to investigate the efficacy and to further confirm the safety of PPCT (ClinicalTrials.gov ID: NCT04435197). Methods: A total of 143 patients with previously untreated, locally advanced, and surgically resectable esophageal squamous cell carcinoma (T2 through T4a, N0 through N+, M0) will be enrolled in PALACE-2. Main exclusion criteria are autoimmune disease, interstitial lung disease, ongoing immunosuppressive therapy, and having received chemotherapy, radiotherapy, target therapy, or immune therapy for this or any other malignancies. Positive programmed cell death ligand 1 expression is not mandatory for enrollment. Patients will receive PPCT, which includes concurrent pembrolizumab (200 mg on day 1 and day 22), carboplatin (area under the curve = 2, once a week for 5 weeks), nab-paclitaxel (50 mg/m2, once a week for 5 weeks), and radiotherapy (23 fractions of 1.8 Gy, 5 fractions a week). Esophagectomy will be performed within 4 to 6 weeks after the completion of PPCT. Results: The primary end point is the rate of pathologic complete response. Secondary outcome measures are 3-year disease-free survival rate, 3-year overall survival rate, R0 resection rate, and adverse events during neoadjuvant and perioperative periods. Conclusions: PPCT was preliminarily demonstrated to be safe, feasible, and to provide potential therapeutic benefits by the PALACE-1 trial. The subsequent multicenter PALACE-2 study will investigate the efficacy and further confirm the safety of PPCT for locally advanced, resectable esophageal squamous cell carcinoma. |
| first_indexed | 2024-12-12T08:07:30Z |
| format | Article |
| id | doaj.art-9170ed1f05874b3b8f9f754f93ff578b |
| institution | Directory Open Access Journal |
| issn | 2666-2736 |
| language | English |
| last_indexed | 2024-12-12T08:07:30Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTCVS Open |
| spelling | doaj.art-9170ed1f05874b3b8f9f754f93ff578b2022-12-22T00:31:54ZengElsevierJTCVS Open2666-27362022-03-019293299Preoperative pembrolizumab combined with chemoradiotherapy for esophageal squamous cell carcinoma: Trial designCentral MessagePerspectiveYuyan Zheng, MD0Chengqiang Li, MD, PhD1Bentong Yu, MD2Shengguang Zhao, MD3Jian Li, MD, PhD4Xiaoyan Chen, MD5Hecheng Li, MD, PhD, FACS6Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Jiangxi, ChinaDepartment of Radiotherapy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaClinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Address for reprints: Hecheng Li, MD, PhD, FACS, Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Rd, Shanghai 200025, China.Objective: The safety and feasibility of preoperative pembrolizumab combined with chemoradiotherapy (PPCT) for resectable esophageal squamous cell carcinoma have been confirmed by the prior Preoperative Anti-PD-1 Antibody combined with Chemoradiotherapy for Locally Advanced Squmous Cell Carcinoma of Esophageus (PALACE)-1 trial. Potential therapeutic benefit was also observed with a pathologic complete response rate of 55.6% after PPCT. We will conduct the multicenter single-arm PALACE-2 study to investigate the efficacy and to further confirm the safety of PPCT (ClinicalTrials.gov ID: NCT04435197). Methods: A total of 143 patients with previously untreated, locally advanced, and surgically resectable esophageal squamous cell carcinoma (T2 through T4a, N0 through N+, M0) will be enrolled in PALACE-2. Main exclusion criteria are autoimmune disease, interstitial lung disease, ongoing immunosuppressive therapy, and having received chemotherapy, radiotherapy, target therapy, or immune therapy for this or any other malignancies. Positive programmed cell death ligand 1 expression is not mandatory for enrollment. Patients will receive PPCT, which includes concurrent pembrolizumab (200 mg on day 1 and day 22), carboplatin (area under the curve = 2, once a week for 5 weeks), nab-paclitaxel (50 mg/m2, once a week for 5 weeks), and radiotherapy (23 fractions of 1.8 Gy, 5 fractions a week). Esophagectomy will be performed within 4 to 6 weeks after the completion of PPCT. Results: The primary end point is the rate of pathologic complete response. Secondary outcome measures are 3-year disease-free survival rate, 3-year overall survival rate, R0 resection rate, and adverse events during neoadjuvant and perioperative periods. Conclusions: PPCT was preliminarily demonstrated to be safe, feasible, and to provide potential therapeutic benefits by the PALACE-1 trial. The subsequent multicenter PALACE-2 study will investigate the efficacy and further confirm the safety of PPCT for locally advanced, resectable esophageal squamous cell carcinoma.http://www.sciencedirect.com/science/article/pii/S2666273621004228esophageal squamous cell carcinomaneoadjuvant therapychemoradiotherapyimmunotherapy |
| spellingShingle | Yuyan Zheng, MD Chengqiang Li, MD, PhD Bentong Yu, MD Shengguang Zhao, MD Jian Li, MD, PhD Xiaoyan Chen, MD Hecheng Li, MD, PhD, FACS Preoperative pembrolizumab combined with chemoradiotherapy for esophageal squamous cell carcinoma: Trial designCentral MessagePerspective JTCVS Open esophageal squamous cell carcinoma neoadjuvant therapy chemoradiotherapy immunotherapy |
| title | Preoperative pembrolizumab combined with chemoradiotherapy for esophageal squamous cell carcinoma: Trial designCentral MessagePerspective |
| title_full | Preoperative pembrolizumab combined with chemoradiotherapy for esophageal squamous cell carcinoma: Trial designCentral MessagePerspective |
| title_fullStr | Preoperative pembrolizumab combined with chemoradiotherapy for esophageal squamous cell carcinoma: Trial designCentral MessagePerspective |
| title_full_unstemmed | Preoperative pembrolizumab combined with chemoradiotherapy for esophageal squamous cell carcinoma: Trial designCentral MessagePerspective |
| title_short | Preoperative pembrolizumab combined with chemoradiotherapy for esophageal squamous cell carcinoma: Trial designCentral MessagePerspective |
| title_sort | preoperative pembrolizumab combined with chemoradiotherapy for esophageal squamous cell carcinoma trial designcentral messageperspective |
| topic | esophageal squamous cell carcinoma neoadjuvant therapy chemoradiotherapy immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2666273621004228 |
| work_keys_str_mv | AT yuyanzhengmd preoperativepembrolizumabcombinedwithchemoradiotherapyforesophagealsquamouscellcarcinomatrialdesigncentralmessageperspective AT chengqianglimdphd preoperativepembrolizumabcombinedwithchemoradiotherapyforesophagealsquamouscellcarcinomatrialdesigncentralmessageperspective AT bentongyumd preoperativepembrolizumabcombinedwithchemoradiotherapyforesophagealsquamouscellcarcinomatrialdesigncentralmessageperspective AT shengguangzhaomd preoperativepembrolizumabcombinedwithchemoradiotherapyforesophagealsquamouscellcarcinomatrialdesigncentralmessageperspective AT jianlimdphd preoperativepembrolizumabcombinedwithchemoradiotherapyforesophagealsquamouscellcarcinomatrialdesigncentralmessageperspective AT xiaoyanchenmd preoperativepembrolizumabcombinedwithchemoradiotherapyforesophagealsquamouscellcarcinomatrialdesigncentralmessageperspective AT hechenglimdphdfacs preoperativepembrolizumabcombinedwithchemoradiotherapyforesophagealsquamouscellcarcinomatrialdesigncentralmessageperspective |