The efficacy and safety of regorafenib/fruquintinib combined with PD-1/PD-L1 for metastatic colorectal cancer: a meta-analysis based on single-arm studies
ObjectiveThe efficacy of regorafenib or fruquintinib in combination with PD-1/PD-L1 inhibitors for metastatic colorectal cancer (mCRC) treatment has not been elucidated. This study aims to systematically evaluate the efficacy and safety of this combination therapy.MethodsPubMed, Embase, Cochrane Lib...
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2025-05-01
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| author | Fan Yang Fan Yang Ying Mao Hanyu Huang Wen Luo Li Liu Wenzhi Chen |
| author_facet | Fan Yang Fan Yang Ying Mao Hanyu Huang Wen Luo Li Liu Wenzhi Chen |
| author_sort | Fan Yang |
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| description | ObjectiveThe efficacy of regorafenib or fruquintinib in combination with PD-1/PD-L1 inhibitors for metastatic colorectal cancer (mCRC) treatment has not been elucidated. This study aims to systematically evaluate the efficacy and safety of this combination therapy.MethodsPubMed, Embase, Cochrane Library, and Web of Science were systematically retrieved until July 24, 2024. A meta-analysis was carried out for the overall objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and the incidence of grade 3 or higher treatment-related adverse events (AEs). Non-overlapping 95% confidence intervals (CIs) were considered statistically significant.Results26 studies encompassing 1,409 patients were analyzed. Pooled analysis revealed an ORR of 6% (95% CI: 3%-12%), a DCR of 62% (95% CI: 55%-68%), a median PFS of 3.84 months (95% CI: 3.19-4.49 months), a median OS of 13.08 months (95% CI: 10.17-16.00 months), and an incidence rate of grade 3–4 AEs of 21% (95% CI: 15%-28%). In subgroup analyses, the fruquintinib-based regimen demonstrated significantly superior efficacy compared to regorafenib-based therapy, with higher ORR (16% [95% CI: 13%-21%] vs 3% [95% CI: 1%-9%]), DCR (79% [95% CI: 72%-85%] vs 54% [95% CI: 47%-61%]), and median PFS (5.40 months [95% CI: 4.60-6.19] vs 3.00 months [95% CI: 2.47-3.52]). Median OS was numerically but not significantly longer with fruquintinib (14.35 months [95% CI: 10.68-18.02] vs 12.70 months [95% CI: 8.79-16.61]). Liver metastasis status strongly influenced outcomes, with significantly lower ORR (3% [95% CI: 1%-13%] vs 49% [95% CI: 32%-76%]) and shorter median PFS (2.37 months [95% CI: 1.77-2.96] vs 3.50 months [95% CI: 3.09-3.91]) in patients with liver involvement.ConclusionThe combination of regorafenib or fruquintinib with PD-1/PD-L1 shows moderate efficacy and acceptable safety in the treatment of mCRC. The fruquintinib-based regimen may be superior to the regorafenib-based regimen, and patients without liver metastasis may derive greater benefits. These findings offer new insights for treating mCRC, although they should be validated through large randomized controlled trials.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42024582268 |
| format | Article |
| id | doaj-art-ca0348e9993e457b9ccecc7e61803af9 |
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| publishDate | 2025-05-01 |
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| spelling | doaj-art-ca0348e9993e457b9ccecc7e61803af92025-08-20T02:34:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15792931579293The efficacy and safety of regorafenib/fruquintinib combined with PD-1/PD-L1 for metastatic colorectal cancer: a meta-analysis based on single-arm studiesFan Yang0Fan Yang1Ying Mao2Hanyu Huang3Wen Luo4Li Liu5Wenzhi Chen6State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, ChinaDepartment of Oncology, Suining Central Hospital, Suining, ChinaDepartment of Oncology, Suining Central Hospital, Suining, ChinaState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, ChinaDepartment of Oncology, Suining Central Hospital, Suining, ChinaDepartment of Oncology, Suining Central Hospital, Suining, ChinaState Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, ChinaObjectiveThe efficacy of regorafenib or fruquintinib in combination with PD-1/PD-L1 inhibitors for metastatic colorectal cancer (mCRC) treatment has not been elucidated. This study aims to systematically evaluate the efficacy and safety of this combination therapy.MethodsPubMed, Embase, Cochrane Library, and Web of Science were systematically retrieved until July 24, 2024. A meta-analysis was carried out for the overall objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and the incidence of grade 3 or higher treatment-related adverse events (AEs). Non-overlapping 95% confidence intervals (CIs) were considered statistically significant.Results26 studies encompassing 1,409 patients were analyzed. Pooled analysis revealed an ORR of 6% (95% CI: 3%-12%), a DCR of 62% (95% CI: 55%-68%), a median PFS of 3.84 months (95% CI: 3.19-4.49 months), a median OS of 13.08 months (95% CI: 10.17-16.00 months), and an incidence rate of grade 3–4 AEs of 21% (95% CI: 15%-28%). In subgroup analyses, the fruquintinib-based regimen demonstrated significantly superior efficacy compared to regorafenib-based therapy, with higher ORR (16% [95% CI: 13%-21%] vs 3% [95% CI: 1%-9%]), DCR (79% [95% CI: 72%-85%] vs 54% [95% CI: 47%-61%]), and median PFS (5.40 months [95% CI: 4.60-6.19] vs 3.00 months [95% CI: 2.47-3.52]). Median OS was numerically but not significantly longer with fruquintinib (14.35 months [95% CI: 10.68-18.02] vs 12.70 months [95% CI: 8.79-16.61]). Liver metastasis status strongly influenced outcomes, with significantly lower ORR (3% [95% CI: 1%-13%] vs 49% [95% CI: 32%-76%]) and shorter median PFS (2.37 months [95% CI: 1.77-2.96] vs 3.50 months [95% CI: 3.09-3.91]) in patients with liver involvement.ConclusionThe combination of regorafenib or fruquintinib with PD-1/PD-L1 shows moderate efficacy and acceptable safety in the treatment of mCRC. The fruquintinib-based regimen may be superior to the regorafenib-based regimen, and patients without liver metastasis may derive greater benefits. These findings offer new insights for treating mCRC, although they should be validated through large randomized controlled trials.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42024582268https://www.frontiersin.org/articles/10.3389/fimmu.2025.1579293/fullmetastatic colorectal cancerregorafenibfruquintinibPD-1/PD-L1 inhibitorsmeta-analysis |
| spellingShingle | Fan Yang Fan Yang Ying Mao Hanyu Huang Wen Luo Li Liu Wenzhi Chen The efficacy and safety of regorafenib/fruquintinib combined with PD-1/PD-L1 for metastatic colorectal cancer: a meta-analysis based on single-arm studies Frontiers in Immunology metastatic colorectal cancer regorafenib fruquintinib PD-1/PD-L1 inhibitors meta-analysis |
| title | The efficacy and safety of regorafenib/fruquintinib combined with PD-1/PD-L1 for metastatic colorectal cancer: a meta-analysis based on single-arm studies |
| title_full | The efficacy and safety of regorafenib/fruquintinib combined with PD-1/PD-L1 for metastatic colorectal cancer: a meta-analysis based on single-arm studies |
| title_fullStr | The efficacy and safety of regorafenib/fruquintinib combined with PD-1/PD-L1 for metastatic colorectal cancer: a meta-analysis based on single-arm studies |
| title_full_unstemmed | The efficacy and safety of regorafenib/fruquintinib combined with PD-1/PD-L1 for metastatic colorectal cancer: a meta-analysis based on single-arm studies |
| title_short | The efficacy and safety of regorafenib/fruquintinib combined with PD-1/PD-L1 for metastatic colorectal cancer: a meta-analysis based on single-arm studies |
| title_sort | efficacy and safety of regorafenib fruquintinib combined with pd 1 pd l1 for metastatic colorectal cancer a meta analysis based on single arm studies |
| topic | metastatic colorectal cancer regorafenib fruquintinib PD-1/PD-L1 inhibitors meta-analysis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1579293/full |
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