{"doi":"10.3389/fonc.2022.917353","title":"Microsatellite stable metastatic colorectal cancer without liver metastasis may be preferred population for regorafenib or fruquintinib plus sintilimab as third-line or above therapy:A real-world study","abstract":"<jats:sec><jats:title>Objectives</jats:title><jats:p>The antitumor activity of nivolumab plus regorafenib in colorectal cancer from a phase Ib REGONIVO study is encouraging. The present study was conducted to evaluate the efficacy and safety of regorafenib or fruquintinib plus sintilimab as third-line or above therapy in patients with microsatellite stable (MSS) metastatic colorectal cancer.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Patients with MSS metastatic colorectal cancer who have failed from prior treatment and received regorafenib or fruquintinib plus sintilimab as third-line or above therapy from January 2019 to December 2020 were prospectively analyzed based on real-world clinical practice. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>42 patients received regorafenib plus sintilimab(RS), and the other 30 patients received fruquintinib plus sintilimab(FS). In the general population, the ORR and DCR were 13.9% and 70.8%, and the median PFS and OS was 4.2(95% CI=2.9-5.5) and 10.5 (95% CI=8.6-12.4) months, respectively. There were no statistically significant differences between RS and FS group in PFS (3.5(2.2-4.8) vs. 5.5(3.5-7.5) months, P=0.434) and OS (11.0(7.0-15.0) vs. 10.5(3.8-17.2) months, P=0.486). Subgroup analysis suggested that patients without liver metastasis responded well to this combination regimen (ORR: 21.4% vs. 9.1%) and obtained better OS (26(8.8-43.2) vs. 10.0(7.4-12.6) months, P=0.016). The incidence of Grade 3-4 adverse events (AEs) was 15.3% and the toxicities were generally tolerable and manageable.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Regorafenib or fruquintinib plus sintilimab as third-line or above therapy provide a feasible treatment regimen for MSS metastatic colorectal cancer with tolerated toxicity. Patients without liver metastasis may be the preferred population for this combination regimen.</jats:p></jats:sec>","journal":"Frontiers in Oncology","year":2022,"id":603852,"datarank":0.47032413238937254,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.0,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":874779,"name":"Huifang Lv","orcid":"0000-0003-0008-3961","position":1,"is_corresponding":false},{"id":606768,"name":"Beibei Chen","orcid":"0000-0001-7772-5171","position":2,"is_corresponding":false},{"id":481047,"name":"Weifeng Xu","orcid":"0000-0003-0096-2288","position":3,"is_corresponding":false},{"id":874780,"name":"Jianzheng Wang","orcid":"0000-0002-2292-3629","position":4,"is_corresponding":false},{"id":1538284,"name":"Yingjun Liu","orcid":"0000-0003-1543-1965","position":5,"is_corresponding":false},{"id":875492,"name":"Saiqi Wang","orcid":null,"position":6,"is_corresponding":false},{"id":349994,"name":"Jing Zhao","orcid":"0000-0001-9480-7638","position":7,"is_corresponding":false},{"id":1549138,"name":"Yunduan He","orcid":null,"position":8,"is_corresponding":false},{"id":1416235,"name":"Xiaobing Chen","orcid":"0000-0001-6074-099X","position":9,"is_corresponding":false},{"id":1549132,"name":"Caiyun Nie","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Microsatellite stable metastatic colorectal cancer without liver metastasis may be preferred population for regorafenib or fruquintinib plus sintilimab as third-line or above therapy:A real-world study","abstract":"<jats:sec><jats:title>Objectives</jats:title><jats:p>The antitumor activity of nivolumab plus regorafenib in colorectal cancer from a phase Ib REGONIVO study is encouraging. The present study was conducted to evaluate the efficacy and safety of regorafenib or fruquintinib plus sintilimab as third-line or above therapy in patients with microsatellite stable (MSS) metastatic colorectal cancer.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Patients with MSS metastatic colorectal cancer who have failed from prior treatment and received regorafenib or fruquintinib plus sintilimab as third-line or above therapy from January 2019 to December 2020 were prospectively analyzed based on real-world clinical practice. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>42 patients received regorafenib plus sintilimab(RS), and the other 30 patients received fruquintinib plus sintilimab(FS). In the general population, the ORR and DCR were 13.9% and 70.8%, and the median PFS and OS was 4.2(95% CI=2.9-5.5) and 10.5 (95% CI=8.6-12.4) months, respectively. There were no statistically significant differences between RS and FS group in PFS (3.5(2.2-4.8) vs. 5.5(3.5-7.5) months, P=0.434) and OS (11.0(7.0-15.0) vs. 10.5(3.8-17.2) months, P=0.486). Subgroup analysis suggested that patients without liver metastasis responded well to this combination regimen (ORR: 21.4% vs. 9.1%) and obtained better OS (26(8.8-43.2) vs. 10.0(7.4-12.6) months, P=0.016). The incidence of Grade 3-4 adverse events (AEs) was 15.3% and the toxicities were generally tolerable and manageable.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Regorafenib or fruquintinib plus sintilimab as third-line or above therapy provide a feasible treatment regimen for MSS metastatic colorectal cancer with tolerated toxicity. Patients without liver metastasis may be the preferred population for this combination regimen.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36226061","pmcid":"PMC9549285","openalex_id":"https://openalex.org/W4297237343","authors":[],"funders":[],"total_grants":0,"fwci":1.766,"citation_percentile":0.87363795,"influential_citations":0,"citation_trend":[{"year":2023,"count":9},{"year":2024,"count":5},{"year":2025,"count":5},{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.frontiersin.org/articles/10.3389/fonc.2022.917353/pdf","host_type":"journal"},{"url":"https://www.frontiersin.org/articles/10.3389/fonc.2022.917353/pdf","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fonc.2022.917353/full","host_type":"publisher"},{"url":"https://doi.org/10.3389/fonc.2022.917353","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36226061","host_type":"repository"},{"url":"https://doaj.org/article/be1252b4efe5496c88e802949ce315b9","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9549285","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9549285","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9549285?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Colorectal Cancer Treatments and Studies","Cancer Immunotherapy and Biomarkers","Colorectal Cancer Surgical Treatments"],"mesh_terms":[],"keywords":["Regorafenib","Medicine","Internal medicine","Colorectal cancer","Clinical endpoint","Population","Metastasis","Oncology","Regimen","Gastroenterology","Phases of clinical research","Cancer","Surgery","Chemotherapy","Clinical trial","Immunotherapy","Targeted Therapy","Liver Metastasis","Microsatellite Stable"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"uniprot"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T22:51:14.579257Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}