Alternating modified CAPOX/CAPIRI plus bevacizumab in untreated unresectable metastatic colorectal cancer: a phase 2 trial
Abstract Previous studies showed encouraging efficacy of alternating FOLFOX/FOLFIRI for metastatic colorectal cancer (mCRC). This phase 2 trial (NCT04324476) aimed to evaluate efficacy and safety of alternating modified CAPOX (capecitabine and oxaliplatin)/modified CAPIRI (capecitabine and irinoteca...
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| Format: | Article |
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Nature Publishing Group
2024-12-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-024-02048-z |
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| author | Sheng Li Xiaoyou Li Hanfeng Xu Jiayuan Huang Jingni Zhu Ying Peng Jun Bao Liangjun Zhu |
| author_facet | Sheng Li Xiaoyou Li Hanfeng Xu Jiayuan Huang Jingni Zhu Ying Peng Jun Bao Liangjun Zhu |
| author_sort | Sheng Li |
| collection | DOAJ |
| description | Abstract Previous studies showed encouraging efficacy of alternating FOLFOX/FOLFIRI for metastatic colorectal cancer (mCRC). This phase 2 trial (NCT04324476) aimed to evaluate efficacy and safety of alternating modified CAPOX (capecitabine and oxaliplatin)/modified CAPIRI (capecitabine and irinotecan) plus bevacizumab (anti-VEGF-A antibody) in untreated unresectable mCRC. Induction treatment included capecitabine 1000 mg/m2 bid D2–8 and D16–22, oxaliplatin 85 mg/m2 D1, irinotecan 150 mg/m2 D15, and bevacizumab 5 mg/kg D1 and 15 for 28-day cycles (up to six cycles). Capecitabine 1000 mg/m2 bid D2–15 and bevacizumab 7.5 mg/kg D1 for 21-day cycles were used as maintenance treatment. 52 patients were included. Median follow-up was 25.0 months. Median progression-free survival (PFS; the primary endpoint) was 11.0 months (95% CI 9.0–12.4). Subgroup analyses showed patients with neutrophil-to-lymphocyte ratio<5 or RAS wild-type disease had longer PFS (both P < 0.05). Objective response and disease control were obtained in 38 (73%; 95% CI 59%–84%) and 49 (94%; 95% CI 84%–99%), respectively. Mean depth of response, conversion and no evidence of disease rates were 46.0% ± 26.3%, 23% and 19%, respectively. Median overall survival was 28.1 months (18.4–34.0). Grade 3–4 treatment-related adverse events (TRAE) occurred in 17 (33%) patients. No treatment-related death was reported. The most common grade 3–4 TRAE were hypertension (13 [25%]), neutrophil count decreased (three [6%]), and hand-foot syndrome (two [4%]). In addition, grade 3–4 TRAE of diarrhea reported in one [2%] patient and no grade 3–4 peripheral neuropathy occurred. Thus, alternating modified CAPOX/CAPIRI plus bevacizumab had promising efficacy and acceptable safety. The regimen may be a novel option for untreated unresectable mCRC. |
| format | Article |
| id | doaj-art-e6542273fc3d47d2917899f7f397e73d |
| institution | OA Journals |
| issn | 2059-3635 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Publishing Group |
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| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-e6542273fc3d47d2917899f7f397e73d2025-08-20T01:56:46ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352024-12-01911710.1038/s41392-024-02048-zAlternating modified CAPOX/CAPIRI plus bevacizumab in untreated unresectable metastatic colorectal cancer: a phase 2 trialSheng Li0Xiaoyou Li1Hanfeng Xu2Jiayuan Huang3Jingni Zhu4Ying Peng5Jun Bao6Liangjun Zhu7Department of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer ResearchDepartment of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer ResearchDepartment of Oncology, The Second Hospital of Nanjing, Nanjing University of Chinese MedicineDepartment of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer ResearchDepartment of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer ResearchDepartment of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer ResearchSenior Health Care Office, Jiangsu Provincial Health CommissionDepartment of Medical Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer ResearchAbstract Previous studies showed encouraging efficacy of alternating FOLFOX/FOLFIRI for metastatic colorectal cancer (mCRC). This phase 2 trial (NCT04324476) aimed to evaluate efficacy and safety of alternating modified CAPOX (capecitabine and oxaliplatin)/modified CAPIRI (capecitabine and irinotecan) plus bevacizumab (anti-VEGF-A antibody) in untreated unresectable mCRC. Induction treatment included capecitabine 1000 mg/m2 bid D2–8 and D16–22, oxaliplatin 85 mg/m2 D1, irinotecan 150 mg/m2 D15, and bevacizumab 5 mg/kg D1 and 15 for 28-day cycles (up to six cycles). Capecitabine 1000 mg/m2 bid D2–15 and bevacizumab 7.5 mg/kg D1 for 21-day cycles were used as maintenance treatment. 52 patients were included. Median follow-up was 25.0 months. Median progression-free survival (PFS; the primary endpoint) was 11.0 months (95% CI 9.0–12.4). Subgroup analyses showed patients with neutrophil-to-lymphocyte ratio<5 or RAS wild-type disease had longer PFS (both P < 0.05). Objective response and disease control were obtained in 38 (73%; 95% CI 59%–84%) and 49 (94%; 95% CI 84%–99%), respectively. Mean depth of response, conversion and no evidence of disease rates were 46.0% ± 26.3%, 23% and 19%, respectively. Median overall survival was 28.1 months (18.4–34.0). Grade 3–4 treatment-related adverse events (TRAE) occurred in 17 (33%) patients. No treatment-related death was reported. The most common grade 3–4 TRAE were hypertension (13 [25%]), neutrophil count decreased (three [6%]), and hand-foot syndrome (two [4%]). In addition, grade 3–4 TRAE of diarrhea reported in one [2%] patient and no grade 3–4 peripheral neuropathy occurred. Thus, alternating modified CAPOX/CAPIRI plus bevacizumab had promising efficacy and acceptable safety. The regimen may be a novel option for untreated unresectable mCRC.https://doi.org/10.1038/s41392-024-02048-z |
| spellingShingle | Sheng Li Xiaoyou Li Hanfeng Xu Jiayuan Huang Jingni Zhu Ying Peng Jun Bao Liangjun Zhu Alternating modified CAPOX/CAPIRI plus bevacizumab in untreated unresectable metastatic colorectal cancer: a phase 2 trial Signal Transduction and Targeted Therapy |
| title | Alternating modified CAPOX/CAPIRI plus bevacizumab in untreated unresectable metastatic colorectal cancer: a phase 2 trial |
| title_full | Alternating modified CAPOX/CAPIRI plus bevacizumab in untreated unresectable metastatic colorectal cancer: a phase 2 trial |
| title_fullStr | Alternating modified CAPOX/CAPIRI plus bevacizumab in untreated unresectable metastatic colorectal cancer: a phase 2 trial |
| title_full_unstemmed | Alternating modified CAPOX/CAPIRI plus bevacizumab in untreated unresectable metastatic colorectal cancer: a phase 2 trial |
| title_short | Alternating modified CAPOX/CAPIRI plus bevacizumab in untreated unresectable metastatic colorectal cancer: a phase 2 trial |
| title_sort | alternating modified capox capiri plus bevacizumab in untreated unresectable metastatic colorectal cancer a phase 2 trial |
| url | https://doi.org/10.1038/s41392-024-02048-z |
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