Efficacy and safety of tyrosine kinase inhibitors combined with chemotherapy versus chemotherapy in advanced non-small cell lung cancer: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

HE Teng ,  LIU Liming , CAO Ru , MENG Qiaoqiao

Department of Respiratory Medicine, the First Affiliated Hospital of Bengbu Medical College, Bengbu, 233000, P.R.China;

Corresponding author：

LIU Liming, Email: BBMcLLm@126.com

Keywords：

Non-small cell lung cancer; Tyrosine kinaseinhibitors; Chemotherapy; Meta-analysis; Randomized controlled trail

DOI：

10.7507/1672-2531.201701070

Video：

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Objective To systematically review the efficacy and safety of tyrosine kinase inhibitors combined with chemotherapy versus chemotherapy in advanced non-small cell lung cancer(NSCLC). Methods An electronically search was conducted in The Cochrane Library, PubMed and EMbase databases from inception to December 2016 to collect randomized controlled trials (RCTs) about tyrosine kinase inhibitors combined with chemotherapy versus chemotherapy for NSCLC. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software. Results A total of 12 RCTs involving 6 559 patients were finally included. The results of meta-analysis showed that: The median progression free survival (PFS) (HR=0.86, 95%CI 0.81 to 0.91, P<0.001) and objective response rate (ORR) (HR=1.43, 95%CI 1.20 to 1.70,P<0.001) of tyrosine kinase inhibitors combined with chemotherapy were significantly longer than those of the chemotherapy group. There were no significant differences between two groups in incidence of median overrall survival (OS) (HR=0.91, 95%CI 0.82 to 1.00,P=0.06), fatigue (RR=1.03, 95%CI 0.97 to 1.11, P=0.33), dyspnea (RR=1.01, 95%CI 0.91 to 1.13, P=0.82) and cough (RR=1.01, 95%CI 0.89 to 1.15, P=0.91). However, the incidence of neutrocytopenia (RR=1.16, 95%CI 1.05 to 1.28, P=0.003), thrombocytopenia (RR=1.46, 95%CI 1.23 to 1.73, P<0.001), diarrhea and hypertension (RR=2.91, 95%CI 2.28 to 3.71,P<0.001) of tyrosine kinase inhibitors combined with chemotherapy group were significantly higher than those of the chemotherapy group. The tyrosine kinase inhibitors combined with chemotherapy group had lower rate of anemia (RR=0.86, 95%CI 0.75 to 0.98,P=0.03). Conclusion Compared with chemotherapy alone, tyrosine kinase inhibitors combined with chemotherapy can improve the median PFS and ORR while it can be used as a treatment for advanced non-small cell lung cancer patients. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.

Citation： HE Teng, LIU Liming, CAO Ru, MENG Qiaoqiao. Efficacy and safety of tyrosine kinase inhibitors combined with chemotherapy versus chemotherapy in advanced non-small cell lung cancer: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2017, 17(10): 1198-1204. doi: 10.7507/1672-2531.201701070 Copy

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18.	Heymach JV, Pazares L, De BF, et al. Randomized phase II study of vandetanib alone or with paclitaxel and carboplatin as first-line treatment for advanced non-small-cell lung cancer. J Clin Oncol, 2008, 26(33): 5407-5415.
19.	王灵杰, 胡雅芳, 汪凤梅. 多靶点酪氨酸激酶抑制剂的研究进展. 中国药房, 2013, 24(13): 1233-1235.0.
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1. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
2. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin, 2011, 61(2): 69-90.
3. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review 1975-2012, National Cancer Institute. Available at: http://seer.cancer.gov/csr/1975_2012/.
4. Han JY, Park K, Kim SW, et al. First-signal: first-line single-agent Iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. J Clin Oncol, 2012, 30(10): 1122-1128.
5. 杨拴盈, 孟夏, 王薇. 多靶点酪氨酸激酶抑制剂在晚期非小细胞肺癌治疗中的是与非. 中华肺部疾病杂志电子版, 2015, 8(6): 1-9.0.
6. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available at: www.cochranehandbook.org.
7. Scagliotti G, Novello S, Von Pawel J, et al. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol, 2010, 28(28): 1835-1842.
8. Pazares LG, Biesma B, Heigener D, et al. Phase III, randomized, double-blind, placebo-controlled trial of gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of advanced, nonsquamous non-small-cell lung cancer. J Clin Oncol, 2012, 30(25): 3084-3092.
9. 王燕, 汪麟, 刘雨桃, 等. 吉西他滨顺铂联合索拉非尼或安慰剂一线治疗晚期非小细胞肺癌的随机对照研究. 中国肺癌杂志, 2011, 14(3): 239-244.0.
10. Reck M, Kaiser R, Mellemgaard A, et al. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol, 2014, 15(2): 143-155.
11. Hanna NH, Kaiser R, Sullivan RN, et al. Nintedanib plus pemetrexed versus placebo plus pemetrexed in patients with relapsed or refractory, advanced non-small cell lung cancer (LUME-Lung 2): a randomized, double-blind, phase III trial. Lung Cancer, 2016, 102:65.
12. Goss GD, Arnold AF, Shepherd FA, et al. Randomized, double-blind trial of carboplatin and paclitaxel with either daily oral cediranib or placebo in advanced non-small-cell lung cancer:NCIC clinical trials group BR24 study. J Clin Oncol, 2010, 28(1): 49-55.
13. Dy GK, Mandrekar SJ, Nelson GD, et al. A randomized phase II study of gemcitabine and carboplatin with or without cediranib as first-line therapy in advanced non-small-cell lung cancer:North Central Cancer Treatment Group Study N0528. J Thorac Oncol, 2013, 8(1): 79-88.
14. Laurie SA, Solomon BJ, Seymour L, et al. Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer:NCIC Clinical Trials Group study BR29. Eur J Cancer, 2014, 50(4): 706-712.
15. de Boer RH, Arrieta O, Yang CH, et al. Vandetanib plus pemetrexed for the second-line treatment of advanced non- small-cell lung cancer:a randomized, double-blind phase Ⅲ trial. J Clin Oncol, 2011, 29(8): 1067-1074.
16. Herbst RS, Sun Y, Eberhardt WE, et al. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol, 2010, 11(7): 619-626.
17. Heymach JV, Johnson BE, Prager D, et al. Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non small-cell lung cancer. J Clin Oncol, 2007, 25(27): 4270-4277.
18. Heymach JV, Pazares L, De BF, et al. Randomized phase II study of vandetanib alone or with paclitaxel and carboplatin as first-line treatment for advanced non-small-cell lung cancer. J Clin Oncol, 2008, 26(33): 5407-5415.
19. 王灵杰, 胡雅芳, 汪凤梅. 多靶点酪氨酸激酶抑制剂的研究进展. 中国药房, 2013, 24(13): 1233-1235.0.
20. Gridelli C, Novello S, Zilembo N, et al. Phase Ⅱ randomized study of vandetanib plus gemcitabine or gemcitabine plus placebo as first-line treatment of advanced non- small- cell lung cancer in elderly patients. J Thorac Oncol, 2014, 9(5): 733-737.
21. Heymach JV, Lockwood SJ, Herbst RS, et al. EGFR biomarkers predict benefit from vandetanib in combination with docetaxel in a randomized phase III study of second-line treatment of patients with advanced non-small cell lung cancer. Ann Oncol, 2014, 25(10): 1941-1948.

Chinese Journal of Evidence-Based Medicine

Efficacy and safety of tyrosine kinase inhibitors combined with chemotherapy versus chemotherapy in advanced non-small cell lung cancer: a meta-analysis

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