Effect of radiotherapy exposure on fruquintinib plus sintilimab treatment in refractory microsatellite stable metastatic colorectal cancer: a prospective observation study
Background Immune checkpoint inhibitors (ICIs) in combination with antiangiogenic drugs have shown promising outcomes in the third-line and subsequent treatments of patients with microsatellite stable metastatic colorectal cancer (MSS-mCRC). Radiotherapy (RT) may enhance the antitumor effect of immu...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2025-01-01
|
| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/1/e009415.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850284653563346944 |
|---|---|
| author | Jing Wang Tao Zhang Lei Zhao Min Jin Pindong Li Shengli Yang Hong Ma Zhenyu Lin Junli Liu Hongli Liu Kunyu Yang Dandan Yu Jianli Hu Jun Xue Mingxia Cheng Chuying Huang |
| author_facet | Jing Wang Tao Zhang Lei Zhao Min Jin Pindong Li Shengli Yang Hong Ma Zhenyu Lin Junli Liu Hongli Liu Kunyu Yang Dandan Yu Jianli Hu Jun Xue Mingxia Cheng Chuying Huang |
| author_sort | Jing Wang |
| collection | DOAJ |
| description | Background Immune checkpoint inhibitors (ICIs) in combination with antiangiogenic drugs have shown promising outcomes in the third-line and subsequent treatments of patients with microsatellite stable metastatic colorectal cancer (MSS-mCRC). Radiotherapy (RT) may enhance the antitumor effect of immunotherapy. However, the effect of RT exposure on patients receiving ICIs and targeted therapy remains unclear. This study aimed to investigate the association between RT exposure and clinical responses to fruquintinib (a highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor) plus sintilimab (an anti-programmed death 1 antibody; F&S) in previously treated patients with MSS-mCRC and to explore predictive biomarkers.Methods In this prospective observational study, patients with mCRC receiving F&S as third-line or subsequent treatment were enrolled. Eligible patients were divided into the RT cohort (RTC) and the non-RT cohort (NRTC) according to their RT history. The primary endpoint was the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Pretreatment fecal and serum samples were collected for microbiome analysis, metabolome analysis, and immune signatures to identify biomarkers for treatment.Results A total of 55 patients were included, of which 25 were in the RTC and 30 in the NRTC. Better ORR (28.0% vs 6.7%, p=0.048), DCR (80.0% vs 36.7%, p=0.002), median PFS (6.2 vs 2.7 months, p<0.001), and median OS (14.8 vs 5.9 months, p=0.019) were noted in patients with RTC than those with NRTC. The enrichment of Lactobacillus, Bifidobacterium, and PC(20:5(5Z,8Z,11Z,14Z,17Z)/20:3(8Z,11Z,14Z)) in RTC significantly predicted better DCR and PFS, whereas guanosine and interleukin-10 predominated in patients with NRTC were negatively correlated with PFS and OS.Conclusions Patients with RT exposure benefited significantly from F&S in the third-line or subsequent treatment for MSS-mCRC. Gut microbiota, metabolites, and cytokines may help predict F&S outcomes for mCRC, which may be helpful in treatment decision-making.Trial registration number ClinicalTrials.gov identifier: NCT05635149. |
| format | Article |
| id | doaj-art-665d8ce5248b4f5a9902ae7b3b6b5baa |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-665d8ce5248b4f5a9902ae7b3b6b5baa2025-08-20T01:47:32ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-01-0113110.1136/jitc-2024-009415Effect of radiotherapy exposure on fruquintinib plus sintilimab treatment in refractory microsatellite stable metastatic colorectal cancer: a prospective observation studyJing Wang0Tao Zhang1Lei Zhao2Min Jin3Pindong Li4Shengli Yang5Hong Ma6Zhenyu Lin7Junli Liu8Hongli Liu9Kunyu Yang10Dandan Yu11Jianli Hu12Jun Xue13Mingxia Cheng14Chuying Huang154 Center for Sleep and Circadian Medicine, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China3 Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, ChinaBristol Myers Squibb Co, Princeton, New Jersey, USA1 Department of Pharmacy, Shanghai Fourth People`s Hospital Affiliated to Tongji University, Shanghai, Shanghai, ChinaInstitute of Radiation Oncology, 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, ChinaThe Yancheng Clinical College of Xuzhou Medical University, The First People`s Hospital of Yancheng, Yancheng, Jiangsu, China2 Institute of Radiation Oncology, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology Cancer Center, Wuhan, China1NeoX Biotech, Shanghai, China1GemPharmatech Co. Ltd., Nanjing, 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, China1 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China1 Cancer 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, ChinaCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaBackground Immune checkpoint inhibitors (ICIs) in combination with antiangiogenic drugs have shown promising outcomes in the third-line and subsequent treatments of patients with microsatellite stable metastatic colorectal cancer (MSS-mCRC). Radiotherapy (RT) may enhance the antitumor effect of immunotherapy. However, the effect of RT exposure on patients receiving ICIs and targeted therapy remains unclear. This study aimed to investigate the association between RT exposure and clinical responses to fruquintinib (a highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor) plus sintilimab (an anti-programmed death 1 antibody; F&S) in previously treated patients with MSS-mCRC and to explore predictive biomarkers.Methods In this prospective observational study, patients with mCRC receiving F&S as third-line or subsequent treatment were enrolled. Eligible patients were divided into the RT cohort (RTC) and the non-RT cohort (NRTC) according to their RT history. The primary endpoint was the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Pretreatment fecal and serum samples were collected for microbiome analysis, metabolome analysis, and immune signatures to identify biomarkers for treatment.Results A total of 55 patients were included, of which 25 were in the RTC and 30 in the NRTC. Better ORR (28.0% vs 6.7%, p=0.048), DCR (80.0% vs 36.7%, p=0.002), median PFS (6.2 vs 2.7 months, p<0.001), and median OS (14.8 vs 5.9 months, p=0.019) were noted in patients with RTC than those with NRTC. The enrichment of Lactobacillus, Bifidobacterium, and PC(20:5(5Z,8Z,11Z,14Z,17Z)/20:3(8Z,11Z,14Z)) in RTC significantly predicted better DCR and PFS, whereas guanosine and interleukin-10 predominated in patients with NRTC were negatively correlated with PFS and OS.Conclusions Patients with RT exposure benefited significantly from F&S in the third-line or subsequent treatment for MSS-mCRC. Gut microbiota, metabolites, and cytokines may help predict F&S outcomes for mCRC, which may be helpful in treatment decision-making.Trial registration number ClinicalTrials.gov identifier: NCT05635149.https://jitc.bmj.com/content/13/1/e009415.full |
| spellingShingle | Jing Wang Tao Zhang Lei Zhao Min Jin Pindong Li Shengli Yang Hong Ma Zhenyu Lin Junli Liu Hongli Liu Kunyu Yang Dandan Yu Jianli Hu Jun Xue Mingxia Cheng Chuying Huang Effect of radiotherapy exposure on fruquintinib plus sintilimab treatment in refractory microsatellite stable metastatic colorectal cancer: a prospective observation study Journal for ImmunoTherapy of Cancer |
| title | Effect of radiotherapy exposure on fruquintinib plus sintilimab treatment in refractory microsatellite stable metastatic colorectal cancer: a prospective observation study |
| title_full | Effect of radiotherapy exposure on fruquintinib plus sintilimab treatment in refractory microsatellite stable metastatic colorectal cancer: a prospective observation study |
| title_fullStr | Effect of radiotherapy exposure on fruquintinib plus sintilimab treatment in refractory microsatellite stable metastatic colorectal cancer: a prospective observation study |
| title_full_unstemmed | Effect of radiotherapy exposure on fruquintinib plus sintilimab treatment in refractory microsatellite stable metastatic colorectal cancer: a prospective observation study |
| title_short | Effect of radiotherapy exposure on fruquintinib plus sintilimab treatment in refractory microsatellite stable metastatic colorectal cancer: a prospective observation study |
| title_sort | effect of radiotherapy exposure on fruquintinib plus sintilimab treatment in refractory microsatellite stable metastatic colorectal cancer a prospective observation study |
| url | https://jitc.bmj.com/content/13/1/e009415.full |
| work_keys_str_mv | AT jingwang effectofradiotherapyexposureonfruquintinibplussintilimabtreatmentinrefractorymicrosatellitestablemetastaticcolorectalcanceraprospectiveobservationstudy AT taozhang effectofradiotherapyexposureonfruquintinibplussintilimabtreatmentinrefractorymicrosatellitestablemetastaticcolorectalcanceraprospectiveobservationstudy AT leizhao effectofradiotherapyexposureonfruquintinibplussintilimabtreatmentinrefractorymicrosatellitestablemetastaticcolorectalcanceraprospectiveobservationstudy AT minjin effectofradiotherapyexposureonfruquintinibplussintilimabtreatmentinrefractorymicrosatellitestablemetastaticcolorectalcanceraprospectiveobservationstudy AT pindongli effectofradiotherapyexposureonfruquintinibplussintilimabtreatmentinrefractorymicrosatellitestablemetastaticcolorectalcanceraprospectiveobservationstudy AT shengliyang effectofradiotherapyexposureonfruquintinibplussintilimabtreatmentinrefractorymicrosatellitestablemetastaticcolorectalcanceraprospectiveobservationstudy AT hongma effectofradiotherapyexposureonfruquintinibplussintilimabtreatmentinrefractorymicrosatellitestablemetastaticcolorectalcanceraprospectiveobservationstudy AT zhenyulin effectofradiotherapyexposureonfruquintinibplussintilimabtreatmentinrefractorymicrosatellitestablemetastaticcolorectalcanceraprospectiveobservationstudy AT junliliu effectofradiotherapyexposureonfruquintinibplussintilimabtreatmentinrefractorymicrosatellitestablemetastaticcolorectalcanceraprospectiveobservationstudy AT hongliliu effectofradiotherapyexposureonfruquintinibplussintilimabtreatmentinrefractorymicrosatellitestablemetastaticcolorectalcanceraprospectiveobservationstudy AT kunyuyang effectofradiotherapyexposureonfruquintinibplussintilimabtreatmentinrefractorymicrosatellitestablemetastaticcolorectalcanceraprospectiveobservationstudy AT dandanyu effectofradiotherapyexposureonfruquintinibplussintilimabtreatmentinrefractorymicrosatellitestablemetastaticcolorectalcanceraprospectiveobservationstudy AT jianlihu effectofradiotherapyexposureonfruquintinibplussintilimabtreatmentinrefractorymicrosatellitestablemetastaticcolorectalcanceraprospectiveobservationstudy AT junxue effectofradiotherapyexposureonfruquintinibplussintilimabtreatmentinrefractorymicrosatellitestablemetastaticcolorectalcanceraprospectiveobservationstudy AT mingxiacheng effectofradiotherapyexposureonfruquintinibplussintilimabtreatmentinrefractorymicrosatellitestablemetastaticcolorectalcanceraprospectiveobservationstudy AT chuyinghuang effectofradiotherapyexposureonfruquintinibplussintilimabtreatmentinrefractorymicrosatellitestablemetastaticcolorectalcanceraprospectiveobservationstudy |