{"title":"Comparative efficacy and safety of first-line tyrosine kinase inhibitors in chronic myeloid leukemia: a systematic review and network meta-analysis.","authors":"Jing-Jing Zhang, Yu-Lan Qian, Zi-Yang Wu, Yue Li, Ying-Jie Guan, Cui Sun, Kai-Li Fu, Tong-Lin Mei, Gaurav Goyal, Paolo Bernasconi, Daniela Damiani, Jian-Guo Zhu","doi":"10.21037/tcr-24-747","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Tyrosine kinase inhibitors (TKIs) have become the preferred drugs for the treatment of chronic phase (CP) chronic myeloid leukemia (CML). This study aims to compare the safety and efficacy of different TKIs as first-line treatments for CML using network meta-analysis (NMA), providing a basis for the precise clinical use of TKIs.</p><p><strong>Methods: </strong>A systematic search was conducted on PubMed, Cochrane Library, Embase, China National knowledge Infrastructure (CNKI), Wanfang, Chinese Science and Technology Periodical Databases (VIP), SinoMed and ClinicalTrials.gov to include RCTs that compared the different TKIs as first line treatment for CML. The search timeline was from inception to 21 July 2023. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the frequentist NMA methods, the efficacy and safety of different TKIs were compared, including the rates of major molecular response (MMR), complete cytogenetic response (CCyR), all grade adverse events, grade 3 or higher hematologic adverse events and liver toxicity.</p><p><strong>Results: </strong>A total of 25 RCTs involving 6,823 patients with CML and 6 types of TKIs were included. In terms of efficacy, second-generation TKIs such as dasatinib, nilotinib, and radotinib showed certain advantages in improving patients' MMR and CCyR compared to imatinib. Additionally, imatinib 800 mg provided better MMRs and CCyRs than imatinib 400 mg. As far as safety was concerned, there was no significant difference in the incidence of all grade adverse events among the different TKIs. All TKIs can cause serious grade 3-4 hematologic adverse events, including anemia, thrombocytopenia, and neutropenia. Dasatinib more likely caused anemia, bosutinib thrombocytopenia, and imatinib neutropenia, whereas nilotinib and flumatinib might have better safety profiles in terms of severe hematologic adverse events. For liver toxicity, radotinib 400 mg and imatinib 800 mg, respectively, had the highest likelihood of ranking first in incidence rates of all grade ALT and AST elevation.</p><p><strong>Conclusions: </strong>In CML, second-generation TKIs are more clinically effective than imatinib even if this last drug has a relatively better safety profile. Thus, as each second-generation TKI has a distinct clinical efficacy and safety, and is associated with different economic factors, its choice should be dictated by the specific patient clinical conditions (patient's specific disease characteristics, comorbid conditions, potential drug interactions, as well as their adherence). Nevertheless, due to the limited number of original research, additional high-quality studies are needed to achieve any firm conclusion on which second-generation TKI is the best choice for that peculiar patient.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11319984/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tcr-24-747","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/26 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Tyrosine kinase inhibitors (TKIs) have become the preferred drugs for the treatment of chronic phase (CP) chronic myeloid leukemia (CML). This study aims to compare the safety and efficacy of different TKIs as first-line treatments for CML using network meta-analysis (NMA), providing a basis for the precise clinical use of TKIs.
Methods: A systematic search was conducted on PubMed, Cochrane Library, Embase, China National knowledge Infrastructure (CNKI), Wanfang, Chinese Science and Technology Periodical Databases (VIP), SinoMed and ClinicalTrials.gov to include RCTs that compared the different TKIs as first line treatment for CML. The search timeline was from inception to 21 July 2023. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the frequentist NMA methods, the efficacy and safety of different TKIs were compared, including the rates of major molecular response (MMR), complete cytogenetic response (CCyR), all grade adverse events, grade 3 or higher hematologic adverse events and liver toxicity.
Results: A total of 25 RCTs involving 6,823 patients with CML and 6 types of TKIs were included. In terms of efficacy, second-generation TKIs such as dasatinib, nilotinib, and radotinib showed certain advantages in improving patients' MMR and CCyR compared to imatinib. Additionally, imatinib 800 mg provided better MMRs and CCyRs than imatinib 400 mg. As far as safety was concerned, there was no significant difference in the incidence of all grade adverse events among the different TKIs. All TKIs can cause serious grade 3-4 hematologic adverse events, including anemia, thrombocytopenia, and neutropenia. Dasatinib more likely caused anemia, bosutinib thrombocytopenia, and imatinib neutropenia, whereas nilotinib and flumatinib might have better safety profiles in terms of severe hematologic adverse events. For liver toxicity, radotinib 400 mg and imatinib 800 mg, respectively, had the highest likelihood of ranking first in incidence rates of all grade ALT and AST elevation.
Conclusions: In CML, second-generation TKIs are more clinically effective than imatinib even if this last drug has a relatively better safety profile. Thus, as each second-generation TKI has a distinct clinical efficacy and safety, and is associated with different economic factors, its choice should be dictated by the specific patient clinical conditions (patient's specific disease characteristics, comorbid conditions, potential drug interactions, as well as their adherence). Nevertheless, due to the limited number of original research, additional high-quality studies are needed to achieve any firm conclusion on which second-generation TKI is the best choice for that peculiar patient.
期刊介绍:
Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.