Safety of first-line systemic therapy in patients with metastatic colorectal cancer: a network meta-analysis of randomized controlled trials

• Published in: BMC cancer 2024-07, Vol.24 (1), p.893-17, Article 893
• Main Authors: Zhan, Yanrong, Cheng, Xianwen, Mei, Pingping, Tan, Shufa, Feng, Wenzhe, Jiang, Hua
• Format: Article
• Language: English
• Subjects: Adverse and side effects; Adverse events; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Bevacizumab - administration & dosage; Bevacizumab - adverse effects; Bevacizumab - therapeutic use; Bias; Cancer; Cancer therapies; Capecitabine - administration & dosage; Capecitabine - adverse effects; Capecitabine - therapeutic use; Case reports; Cetuximab - administration & dosage; Cetuximab - adverse effects; Cetuximab - therapeutic use; Chemotherapy; Clinical trials; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Comparative analysis; Complications and side effects; Computer programs; Diarrhea; Drug therapy; Drugs; First-line; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Fluorouracil - therapeutic use; Humans; Leucovorin - administration & dosage; Leucovorin - adverse effects; Leucovorin - therapeutic use; Medical prognosis; Meta-analysis; Metastases; Metastasis; Metastatic colorectal cancer; Methods; Neoplasm Metastasis; Network Meta-Analysis; Neuropathy; Neutropenia; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - adverse effects; Organoplatinum Compounds - therapeutic use; Oxaliplatin; Oxaliplatin - administration & dosage; Oxaliplatin - adverse effects; Oxaliplatin - therapeutic use; Panitumumab - administration & dosage; Panitumumab - adverse effects; Panitumumab - therapeutic use; Peripheral neuropathy; Quality of life; Randomized Controlled Trials as Topic; Risk assessment; Safety; Statistical analysis; Systemic therapy; Thrombocytopenia; Toxicity
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-024-12662-3

To evaluate the safety of first-line systemic therapy for metastatic colorectal cancer through network meta-analysis. The literature from PubMed, Embase, Web of Science, and Cochrane Library databases was searched from the inception of the databases to August 15, 2023, and strict inclusion and exclusion criteria were applied to screen studies. The Cochrane Bias Risk Assessment Tool (RoB 2.0) was used to evaluate the quality of the included literature. Network meta-analysis was conducted using Stata 15.0 and R4.3.1 software to compare the incidence of adverse events (AEs) among different treatment regimens. A total of 53 randomized controlled trials, involving 17,351 patients with metastatic colorectal cancer (mCRC), were ultimately included, encompassing 29 different therapeutic approaches. According to SUCRA rankings, the CAPOX regimen is most likely to rank first in terms of safety, while the FOLFOXIRI + panitumumab regimen is most likely to rank last. In terms of specific AEs, the CAPOX regimen, whether used alone or in combination with targeted drugs (bevacizumab and cetuximab), is associated with a reduced risk of neutropenia and febrile neutropenia, as well as an increased risk of thrombocytopenia and diarrhea. The FOLFOX regimen, with or without bevacizumab, is linked to an increased risk of neutropenia and peripheral sensory neuropathy. The FOLFIRI/CAPIRI + bevacizumab regimen is associated with a reduced risk of peripheral sensory neuropathy. S-1 and S-1 + oxaliplatin are well-tolerated in terms of gastrointestinal reactions. The FOLFOXIRI regimen, whether used alone or in combination with targeted drugs, is associated with various AEs. In summary, the CAPOX regimen may be the safest option among the first-line systemic treatment regimens for mCRC patients, while the FOLFOXIRI + panitumumab regimen may be associated with a higher incidence of grade 3 or higher AEs.