Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer
Background In locally advanced rectal cancer (LARC), preoperative short-course radiotherapy (SCRT) with delayed surgery has been shown to be as effective as long-course chemoradiotherapy, with only modest benefits. This study aimed to evaluate the efficacy and safety of preoperative SCRT combined wi...
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BMJ Publishing Group
2021-11-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/9/11/e003554.full |
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| author | Jun Fan Jing Wang Tao Zhang Xin Li Lan Zhang Zheng Wang Tao Liu Gang Li Peng Zhang Chi Ma Ming Cai Gang Wu Zhenyu Lin Kailin Cai Xiu Nie Junli Liu Hongli Liu Weikang Zhang Jingbo Gao Chuanqing Wu Linfang Wang Zhiguo Hou Kunyu Yang Kaixiong Tao |
| author_facet | Jun Fan Jing Wang Tao Zhang Xin Li Lan Zhang Zheng Wang Tao Liu Gang Li Peng Zhang Chi Ma Ming Cai Gang Wu Zhenyu Lin Kailin Cai Xiu Nie Junli Liu Hongli Liu Weikang Zhang Jingbo Gao Chuanqing Wu Linfang Wang Zhiguo Hou Kunyu Yang Kaixiong Tao |
| author_sort | Jun Fan |
| collection | DOAJ |
| description | Background In locally advanced rectal cancer (LARC), preoperative short-course radiotherapy (SCRT) with delayed surgery has been shown to be as effective as long-course chemoradiotherapy, with only modest benefits. This study aimed to evaluate the efficacy and safety of preoperative SCRT combined with subsequent CAPOX (capecitabine and oxaliplatin) and the anti-PD-1 antibody camrelizumab in patients with LARC.Methods This was a prospective, single-arm, phase II trial. Treatment-naïve patients with histologically confirmed T3-4N0M0 or T1-4N+M0 rectal adenocarcinoma received 5×5 Gy SCRT with two subsequent 21-day cycles of CAPOX plus camrelizumab after 1 week, followed by radical surgery after 1 week. The primary endpoint was pathological complete response (pCR) rate. Biomarker analysis was performed to identify a potential predictor of pCR to treatment.Results From November 7, 2019 to September 14, 2020, 30 patients were enrolled, and 27 patients received at least one dose of CAPOX plus camrelizumab. Surgery was performed in 27 (100%) patients. The pCR (ypT0N0) rate was 48.1% (13/27), including 46.2% (12/26) for proficient mismatch repair (MMR) tumors and 100% (1/1) for deficient MMR tumors. Immune-related adverse events were all grade 1–2, with the most common being reactive cutaneous capillary endothelial proliferation (81.5%). No grade 4/5 adverse events occurred. Biomarker analysis showed patients without FGFR1–3 deletions had a better tendency for pCR.Conclusions SCRT combined with subsequent CAPOX plus camrelizumab followed by delayed surgery showed a favorable pCR rate with good tolerance in patients with LARC, especially in the proficient MMR setting. A randomized controlled trial is ongoing to confirm these results.Trial registration number ClinicalTrials.gov identifier: NCT04231552. |
| format | Article |
| id | doaj-art-62ef251d08c74b86bd20fda520aa0e5f |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2021-11-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-62ef251d08c74b86bd20fda520aa0e5f2025-02-03T21:05:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-11-0191110.1136/jitc-2021-003554Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancerJun Fan0Jing Wang1Tao Zhang2Xin Li3Lan Zhang4Zheng Wang5Tao Liu6Gang Li7Peng Zhang8Chi Ma9Ming Cai10Gang Wu11Zhenyu Lin12Kailin Cai13Xiu Nie14Junli Liu15Hongli Liu16Weikang Zhang17Jingbo Gao18Chuanqing Wu19Linfang Wang20Zhiguo Hou21Kunyu Yang22Kaixiong Tao23Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China3 Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, ChinaDepartment of Pharmacy, The Second People`s Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu, ChinaKey Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China1Shanghai Jiliang Biotechnology Inc, Shanghai, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Neurosurgery, Xuanwu Hospital Capital Medical University, Beijing, ChinaDepartment of Medical Affairs, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China1NeoX Biotech, Shanghai, China1GemPharmatech Co. Ltd., Nanjing, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Medical Affairs, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaBackground In locally advanced rectal cancer (LARC), preoperative short-course radiotherapy (SCRT) with delayed surgery has been shown to be as effective as long-course chemoradiotherapy, with only modest benefits. This study aimed to evaluate the efficacy and safety of preoperative SCRT combined with subsequent CAPOX (capecitabine and oxaliplatin) and the anti-PD-1 antibody camrelizumab in patients with LARC.Methods This was a prospective, single-arm, phase II trial. Treatment-naïve patients with histologically confirmed T3-4N0M0 or T1-4N+M0 rectal adenocarcinoma received 5×5 Gy SCRT with two subsequent 21-day cycles of CAPOX plus camrelizumab after 1 week, followed by radical surgery after 1 week. The primary endpoint was pathological complete response (pCR) rate. Biomarker analysis was performed to identify a potential predictor of pCR to treatment.Results From November 7, 2019 to September 14, 2020, 30 patients were enrolled, and 27 patients received at least one dose of CAPOX plus camrelizumab. Surgery was performed in 27 (100%) patients. The pCR (ypT0N0) rate was 48.1% (13/27), including 46.2% (12/26) for proficient mismatch repair (MMR) tumors and 100% (1/1) for deficient MMR tumors. Immune-related adverse events were all grade 1–2, with the most common being reactive cutaneous capillary endothelial proliferation (81.5%). No grade 4/5 adverse events occurred. Biomarker analysis showed patients without FGFR1–3 deletions had a better tendency for pCR.Conclusions SCRT combined with subsequent CAPOX plus camrelizumab followed by delayed surgery showed a favorable pCR rate with good tolerance in patients with LARC, especially in the proficient MMR setting. A randomized controlled trial is ongoing to confirm these results.Trial registration number ClinicalTrials.gov identifier: NCT04231552.https://jitc.bmj.com/content/9/11/e003554.full |
| spellingShingle | Jun Fan Jing Wang Tao Zhang Xin Li Lan Zhang Zheng Wang Tao Liu Gang Li Peng Zhang Chi Ma Ming Cai Gang Wu Zhenyu Lin Kailin Cai Xiu Nie Junli Liu Hongli Liu Weikang Zhang Jingbo Gao Chuanqing Wu Linfang Wang Zhiguo Hou Kunyu Yang Kaixiong Tao Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer Journal for ImmunoTherapy of Cancer |
| title | Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer |
| title_full | Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer |
| title_fullStr | Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer |
| title_full_unstemmed | Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer |
| title_short | Phase II, single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer |
| title_sort | phase ii single arm trial of preoperative short course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer |
| url | https://jitc.bmj.com/content/9/11/e003554.full |
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