Efficacy and safety of flumatinib for chronic myelocytic leukemia: a network meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

LI Xue ¹ , LI Rui ^2,3,4 , LI Meixuan ^2,3,4 , HOU Liangying ^2,3,4 , FU Jiani ^3,4,5 , ZHANG Wenhao ^3,4,6 ,  ZHAO Kun ¹ ,  YANG Kehu ^2,3,4

1. China National Health Development Research Center, Beijing 100044, P.R.China;
2. Evidence Based Social Science Research Center, School of Public Health, Lanzhou University, Lanzhou 730000, P.R.China;
3. Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, P.R.China;
4. Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou 730000, P.R.China;
5. The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, P.R.China;
6. The Second School of Clinical Medicine, Lanzhou University, Lanzhou 730000, P.R.China;

Corresponding author：

ZHAO Kun, Email: zk317@nhei.cn; YANG Kehu, Email: kehuyangebm2006@126.com

Keywords：

Tyrosine kinase inhibitor; Chronic myelocytic leukemia; Network meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.202101003

Video：

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Objective To systematically review the efficacy and safety of different tyrosine kinase inhibitors (TKIs) in the treatment of chronic myelocytic leukemia (CML).Methods PubMed, EMbase, The Cochrane Library, CBM, WanFang Data and CNKI databases were electronically searched to collect randomized controlled trials (RCTs) of nilotinib, dasatinib, flumatinib and imatinib for CML from inception to August, 2020. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies; network meta-analysis was then performed using Stata 15.0 software and R 3.4.0 software.Results A total of 8 RCTs involving 2 775 patients were included. Compared with other TKIs, flumatinib had higher 3-month early molecular response and 1-year progression free survival, and the incidence of serious side effects was relatively low. Major molecular response and complete cytogenetic response were significantly superior to imatinib, and had the same or similar effects to other second-generation TKIs.Conclusions Current evidence shows that flumartinib in the treatment of CML is obviously superior to imatinib, has the same or similar effect with other second generation TKIs. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusions.

Citation： LI Xue, LI Rui, LI Meixuan, HOU Liangying, FU Jiani, ZHANG Wenhao, ZHAO Kun, YANG Kehu. Efficacy and safety of flumatinib for chronic myelocytic leukemia: a network meta-analysis. Chinese Journal of Evidence-Based Medicine, 2021, 21(7): 816-824. doi: 10.7507/1672-2531.202101003 Copy

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2.	Apperley JF. Chronic myeloid leukaemia. Lancet, 2015, 385(9976): 1447-1459.
3.	贺其图, 时风桐. 包头市白血病流行病学调查. 内蒙古医学杂志, 1993, (2): 5-7.
4.	张新友, 张大龙, 孙璇, 等. 深圳特区白血病与再生障碍性贫血的流行病学调查. 中华血液学杂志, 2001, 22(7): 347.
5.	胡进林, 冒镇, 董德平, 等. 海安县 15 年白血病流行病学调查. 中国交通医学杂志, 2004, 18(1): 114-115.
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8.	中华医学会血液学分会. 慢性髓性白血病中国诊断与治疗指南(2020 年版). 中华血液学杂志, 2020, 41(5): 353-364.
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10.	Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med, 2010, 362(24): 2251-2259.
11.	Zhang L, Meng L, Liu B, et al. Flumatinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia: a phase iii, randomized, open-label, multi-center festnd study. Clin Cancer Res, 2021, 27(1): 70-77.
12.	Pan B, Wu Y, Yang Q, et al. The impact of major dietary patterns on glycemic control, cardiovascular risk factors, and weight loss in patients with type 2 diabetes: a network meta-analysis. J Evid Based Med, 2019, 12(1): 29-39.
13.	Grant RL. The uptake of Bayesian methods in biomedical meta-analyses: A scoping review (2005-2016). J Evid Based Med, 2019, 12(1): 69-75.
14.	Signorovitch J, Ayyagari R, Reichmann WM, et al. Major molecular response during the first year of dasatinib, imatinib or nilotinib treatment for newly diagnosed chronic myeloid leukemia: a network meta-analysis. Cancer Treat Rev, 2014, 40(2): 285-292.
15.	Mealing S, Barcena L, Hawkins N, et al. The relative efficacy of imatinib, dasatinib and nilotinib for newly diagnosed chronic myeloid leukemia: a systematic review and network meta-analysis. Exp Hematol Oncol, 2013, 2(1): 5.
16.	Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med, 2015, 162(11): 777-784.
17.	Higgins JPT, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions version 6.1 (updated September 2020). Available at: www.training.cochrane.org/handbook.
18.	易跃雄, 张蔚, 刘小媛, 等. 网状 Meta 分析图形结果解读. 中国循证医学杂志, 2015, 15(1): 103-109.
19.	张慧芳, 马金沙, 李璐, 等. EGFR-TKIs 一线治疗晚期非小细胞肺癌的有效性和安全性比较: 网状Meta分析. 中华疾病控制杂志, 2020, 24(2): 92-98.
20.	Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol, 2011, 64(2): 163-171.
21.	Hjorth-Hansen H, Stenke L, Söderlund S, et al. Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006). Eur J Haematol, 2015, 94(3): 243-250.
22.	Chuah CT, Nakamae H, Shen ZX, et al. Efficacy and safety of dasatinib versus imatinib in the East Asian subpopulation of the DASISION trial of newly diagnosed chronic myeloid leukemia in chronic phase. Leuk Lymphoma, 2014, 55(9): 2093-2100.
23.	Radich JP, Kopecky KJ, Appelbaum FR, et al. A randomized trial of dasatinib 100 mg versus imatinib 400 mg in newly diagnosed chronic-phase chronic myeloid leukemia. Blood, 2012, 120(19): 3898-3905.
24.	Wang J, Shen ZX, Saglio G, et al. Phase 3 study of nilotinib vs imatinib in Chinese patients with newly diagnosed chronic myeloid leukemia in chronic phase: ENESTchina. Blood, 2015, 125(18): 2771-2778.
25.	Cortes JE, De Souza CA, Ayala M, et al. Switching to nilotinib versus imatinib dose escalation in patients with chronic myeloid leukaemia in chronic phase with suboptimal response to imatinib (LASOR): a randomised, open-label trial. Lancet Haematol, 2016, 3(12): e581-e591.
26.	Jabbour E, Kantarjian HM, Saglio G, et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood, 2014, 123(4): 494-500.
27.	Larson RA, Hochhaus A, Hughes TP, et al. Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up. Leukemia, 2012, 26(10): 2197-2203.
28.	Hochhaus A, Saglio G, Hughes TP, et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia, 2016, 30(5): 1044-1054.
29.	Cortes JE, Saglio G, Kantarjian HM, et al. Final 5-Year Study Results of DASISION: the dasatinib versus imatinib study in treatment-naïve chronic myeloid leukemia patients trial. J Clin Oncol, 2016, 34(20): 2333-2340.
30.	Cortes JE, Jiang Q, Wang J, et al. Dasatinib vs. imatinib in patients with chronic myeloid leukemia in chronic phase (CML-CP) who have not achieved an optimal response to 3 months of imatinib therapy: the DASCERN randomized study. Leukemia, 2020, 34(8): 2064-2073.
31.	Nakamae H, Fujisawa S, Ogura M, et al. Dasatinib versus imatinib in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia: a subanalysis of the DASISION 5-year final report. Int J Hematol, 2017, 105(6): 792-804.
32.	姜金方, 陈笑艳, 钟大放. 我国研发的小分子酪氨酸激酶抑制剂的药物代谢研究. 药学学报, 2016, 51(2): 248-256.
33.	张晓瀚, 杜新, 蔡云, 等. 尼洛替尼治疗伊马替尼耐药的慢性髓系白血病加速期疗效分析(附 1 例报告). 临床血液学杂志, 2011, 24(6): 680-682.
34.	Carneiro BA, Kaplan JB, Giles FJ. Tyrosine kinase inhibitor therapy in chronic myeloid leukemia: update on key adverse events. Expert Rev Hematol, 2015, 8(4): 457-479.

1. O'Brien S, Berman E, Borghaei H, et al. NCCN clinical practice guidelines in oncology: chronic myelogenous leukemia. J Natl Compr Canc Netw, 2009, 7(9): 984-1023.
2. Apperley JF. Chronic myeloid leukaemia. Lancet, 2015, 385(9976): 1447-1459.
3. 贺其图, 时风桐. 包头市白血病流行病学调查. 内蒙古医学杂志, 1993, (2): 5-7.
4. 张新友, 张大龙, 孙璇, 等. 深圳特区白血病与再生障碍性贫血的流行病学调查. 中华血液学杂志, 2001, 22(7): 347.
5. 胡进林, 冒镇, 董德平, 等. 海安县 15 年白血病流行病学调查. 中国交通医学杂志, 2004, 18(1): 114-115.
6. 中华医学会血液学分会. 中国慢性髓性白血病诊断与治疗指南(2013 年版). 中华血液学杂志, 2013, 34(5): 464-470.
7. Hochhaus A, Larson RA, Guilhot F, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med, 2017, 376(10): 917-927.
8. 中华医学会血液学分会. 慢性髓性白血病中国诊断与治疗指南(2020 年版). 中华血液学杂志, 2020, 41(5): 353-364.
9. Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med, 2010, 362(24): 2260-2270.
10. Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med, 2010, 362(24): 2251-2259.
11. Zhang L, Meng L, Liu B, et al. Flumatinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia: a phase iii, randomized, open-label, multi-center festnd study. Clin Cancer Res, 2021, 27(1): 70-77.
12. Pan B, Wu Y, Yang Q, et al. The impact of major dietary patterns on glycemic control, cardiovascular risk factors, and weight loss in patients with type 2 diabetes: a network meta-analysis. J Evid Based Med, 2019, 12(1): 29-39.
13. Grant RL. The uptake of Bayesian methods in biomedical meta-analyses: A scoping review (2005-2016). J Evid Based Med, 2019, 12(1): 69-75.
14. Signorovitch J, Ayyagari R, Reichmann WM, et al. Major molecular response during the first year of dasatinib, imatinib or nilotinib treatment for newly diagnosed chronic myeloid leukemia: a network meta-analysis. Cancer Treat Rev, 2014, 40(2): 285-292.
15. Mealing S, Barcena L, Hawkins N, et al. The relative efficacy of imatinib, dasatinib and nilotinib for newly diagnosed chronic myeloid leukemia: a systematic review and network meta-analysis. Exp Hematol Oncol, 2013, 2(1): 5.
16. Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med, 2015, 162(11): 777-784.
17. Higgins JPT, Thomas J, Chandler J, et al. Cochrane Handbook for Systematic Reviews of Interventions version 6.1 (updated September 2020). Available at: www.training.cochrane.org/handbook.
18. 易跃雄, 张蔚, 刘小媛, 等. 网状 Meta 分析图形结果解读. 中国循证医学杂志, 2015, 15(1): 103-109.
19. 张慧芳, 马金沙, 李璐, 等. EGFR-TKIs 一线治疗晚期非小细胞肺癌的有效性和安全性比较: 网状Meta分析. 中华疾病控制杂志, 2020, 24(2): 92-98.
20. Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol, 2011, 64(2): 163-171.
21. Hjorth-Hansen H, Stenke L, Söderlund S, et al. Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006). Eur J Haematol, 2015, 94(3): 243-250.
22. Chuah CT, Nakamae H, Shen ZX, et al. Efficacy and safety of dasatinib versus imatinib in the East Asian subpopulation of the DASISION trial of newly diagnosed chronic myeloid leukemia in chronic phase. Leuk Lymphoma, 2014, 55(9): 2093-2100.
23. Radich JP, Kopecky KJ, Appelbaum FR, et al. A randomized trial of dasatinib 100 mg versus imatinib 400 mg in newly diagnosed chronic-phase chronic myeloid leukemia. Blood, 2012, 120(19): 3898-3905.
24. Wang J, Shen ZX, Saglio G, et al. Phase 3 study of nilotinib vs imatinib in Chinese patients with newly diagnosed chronic myeloid leukemia in chronic phase: ENESTchina. Blood, 2015, 125(18): 2771-2778.
25. Cortes JE, De Souza CA, Ayala M, et al. Switching to nilotinib versus imatinib dose escalation in patients with chronic myeloid leukaemia in chronic phase with suboptimal response to imatinib (LASOR): a randomised, open-label trial. Lancet Haematol, 2016, 3(12): e581-e591.
26. Jabbour E, Kantarjian HM, Saglio G, et al. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood, 2014, 123(4): 494-500.
27. Larson RA, Hochhaus A, Hughes TP, et al. Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up. Leukemia, 2012, 26(10): 2197-2203.
28. Hochhaus A, Saglio G, Hughes TP, et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia, 2016, 30(5): 1044-1054.
29. Cortes JE, Saglio G, Kantarjian HM, et al. Final 5-Year Study Results of DASISION: the dasatinib versus imatinib study in treatment-naïve chronic myeloid leukemia patients trial. J Clin Oncol, 2016, 34(20): 2333-2340.
30. Cortes JE, Jiang Q, Wang J, et al. Dasatinib vs. imatinib in patients with chronic myeloid leukemia in chronic phase (CML-CP) who have not achieved an optimal response to 3 months of imatinib therapy: the DASCERN randomized study. Leukemia, 2020, 34(8): 2064-2073.
31. Nakamae H, Fujisawa S, Ogura M, et al. Dasatinib versus imatinib in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia: a subanalysis of the DASISION 5-year final report. Int J Hematol, 2017, 105(6): 792-804.
32. 姜金方, 陈笑艳, 钟大放. 我国研发的小分子酪氨酸激酶抑制剂的药物代谢研究. 药学学报, 2016, 51(2): 248-256.
33. 张晓瀚, 杜新, 蔡云, 等. 尼洛替尼治疗伊马替尼耐药的慢性髓系白血病加速期疗效分析(附 1 例报告). 临床血液学杂志, 2011, 24(6): 680-682.
34. Carneiro BA, Kaplan JB, Giles FJ. Tyrosine kinase inhibitor therapy in chronic myeloid leukemia: update on key adverse events. Expert Rev Hematol, 2015, 8(4): 457-479.

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