Gefitinib versus Pemetrexed as Second-line Treatment for Advanced Non-small Cell Lung Cancer: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 LIUZi-li ,  WANGBin , LIUJi-zhu , LIUWei-wei

Department of Respiratory Diseases, Huaibei Miners General Hospital, Huaibei 235000, China;

Corresponding author：

WANGBin, Email: 2601195353@qq.com

Keywords：

Gefitinib; Pemetrexed; Non-small cell lung cancer; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20160176

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To systematically review the efficacy and safety of gefitinib versus pemetrexed as second-line treatment for advanced non-small cell lung cancer (NSCLC). Methods Databases including PubMed, The Cochrane Library (Issue 4, 2016), EMbase, CNKI, VIP and WanFang Data were searched to collect randomized controlled trials (RCTs) about gefitinib versus pemetrexed as second-line treatment for advanced NSCLC from inception to April 2016. 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 11 RCTs involving 1 005 patients were finally included. The results of meta-analysis showed that: the rate of progression free survival (PFS) in the gefitinib group was superior to the pemetrexed group (HR=0.59, 95%CI 0.47 to 0.73, P<0.000 01). However, there were no significant differences between two groups in overall response rate (RR=1.28, 95%CI 0.86 to 1.90, P=0.22), disease control rate (RR=0.92, 95%CI 0.77 to 1.12, P=0.41) and the rate of overall survival (HR=0.75, 95%CI 0.56 to 1.01, P=0.05). The incidences of skin rash (RR=8.72, 95% CI 3.65 to 20.84, P<0.000 01) and diarrhea (RR=2.87, 95% CI 1.29 to 6.38, P=0.01) were significantly higher, but the incidences of neutropenia (RR=0.12, 95%CI 0.05 to 0.26, P<0.000 01) and fatigue (RR=0.46, 95%CI 0.30 to 0.72, P=0.000 6) were lower in the gefitinib group than those in the pemetrexed group. Conclusion Gefitinib shows more superiority to pemetrexed, and it can be used as the second-line drug for advanced NSCLC． Due to the limited quality and quantity of included studies, more high quality studies are needed to verify the above conclusion.

Citation： LIUZi-li, WANGBin, LIUJi-zhu, LIUWei-wei. Gefitinib versus Pemetrexed as Second-line Treatment for Advanced Non-small Cell Lung Cancer: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2016, 16(10): 1154-1161. doi: 10.7507/1672-2531.20160176 Copy

1.	Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin, 2016, 66(1): 7-30.
2.	Zheng R, Zeng H, Zhang S, et al. National estimates of cancer prevalence in China, 2011. Cancer Lett, 2016, 370(1): 33-38.
3.	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
4.	Xiao HQ, Tian RH, Zhang ZH, et al. Efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell-lung cancer: a systematic review and meta-analysis. Onco Targets Ther, 2016, 9: 1471-1476.
5.	石远凯, 孙燕, 于金明, 等. 中国晚期原发性肺癌诊治专家共识(2016年版). 中国肺癌杂志, 2016, 19(1): 1-15.
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.cochrane-handbook.org..
7.	Kim YS, Cho EK, Woo HS, et al. Randomized Phase II Study of Pemetrexed Versus Gefitinib in Previously Treated Patients with Advanced Non-small Cell Lung Cancer. Cancer Res Treat, 2016, 48(1): 80-87.
8.	Sun JM, Lee KH, Kim SW, et al. Gefitinib versus pemetrexed as second-line treatment in patients with nonsmall cell lung cancer previously treated with platinum-based chemotherapy (KCSG-LU08-01): an open-label, phase 3 trial. Cancer, 2012, 118(24): 6234-6242.
9.	Zhou Q, Cheng Y, Yang JJ, et al. Pemetrexed versus gefitinib as a second-line treatment in advanced nonsquamous nonsmall-cell lung cancer patients harboring wild-type EGFR (CTONG0806): a multicenter randomized trial. Ann Oncol, 2014, 25(12): 2385-2391.
10.	刘孝民. 吉非替尼对比培美曲塞治疗晚期非鳞非小细胞肺癌的临床疗效及安全性评价. 中国临床药理学杂志, 2015, 31(24): 2393-2395.
11.	宋霆婷, 盖慧荣, 李伟, 等. 吉非替尼治疗晚期非小细胞肺癌的疗效观察. 疑难病杂志, 2015, 14(8): 778-781.
12.	张宇卉, 王海宾. 吉非替尼和培美曲塞治疗晚期复发非小细胞肺癌的临床研究. 临床合理用药杂志, 2009, 2(18): 14-16.
13.	张定国, 阮秀丽. 吉非替尼对比培美曲塞二线治疗晚期非小细胞肺癌的临床研究. 癌症进展, 2016, 14(1): 78-80.
14.	张静, 刘素勤, 张洁, 等. 晚期非小细胞肺癌二线治疗不同方案的疗效及成本效益分析. 临床肿瘤学杂志, 2012, 17(10): 908-911.
15.	戴宏宇, 徐玲, 夏春伟, 等. 吉非替尼对比培美曲塞二线治疗晚期非鳞型非小细胞肺癌的随机对照临床研究. 中国肺癌杂志, 2013, 16(8): 405-410.
16.	王美清, 何立香, 彭大为, 等. 培美曲塞与吉非替尼二线治疗晚期NSCLC的对比研究. 中国热带医学, 2012, 12(11): 1361-1363.
17.	赵利红, 汪海岩, 张德芳. 培美曲塞与吉非替尼二线治疗晚期非小细胞肺癌的临床对比分析. 中国肿瘤临床与康复, 2013, 20(11): 1235-1238.
18.	Fang JY, Dong HL, Wu KS, et al. Characteristics and Prediction of Lung Cancer Mortality in China from 1991 to 2013. Asian Pac J Cancer Prev, 2015, 16(14): 5829-5834.
19.	Qin HF, Qu LL, Liu H, et al. Serum CEA level change and its significance before and after Gefitinib therapy on patients with advanced non-small cell lung cancer. Asian Pac J Cancer Prev, 2013, 14(7): 4205-4208.
20.	周欣, 李晓琴, 王秀丽, 等. 吉非替尼获得性耐药的非小细胞肺癌患者临床特点. 中国癌症杂志, 2015, 25(3): 222-230.
21.	谢亚琳, 梁继珍, 苏宁. 吉非替尼与厄洛替尼在EGFR基因敏感突变晚期NSCLC患者一线治疗中的疗效比较. 南方医科大学学报, 2015, 35(3): 446-449.
22.	Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol, 2011, 29(21): 2866-2874.
23.	Rosell R, Moran T, Queralt C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med, 2009, 361(10): 958-967.
24.	Kawano Y, Ohyanagi F, Yanagitani N, et al. Pemetrexed and cisplatin for advanced non-squamous non-small cell lung cancer in Japanese patients: phase II study. Anticancer Res, 2013, 33(8): 3327-3333.
25.	Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol, 2004, 22(9): 1589-1597.
26.	Kim ES, Hirsh V, Mok T, et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet, 2008, 372(9652): 1809-1818.
27.	顾亮, 赵恬, 钦光跃. 吉非替尼对比培美曲塞二线治疗晚期非小细胞肺癌的临床研究. 中国临床药理学与治疗学, 2012, 17(5): 569-573.

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin, 2016, 66(1): 7-30.
2. Zheng R, Zeng H, Zhang S, et al. National estimates of cancer prevalence in China, 2011. Cancer Lett, 2016, 370(1): 33-38.
3. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
4. Xiao HQ, Tian RH, Zhang ZH, et al. Efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell-lung cancer: a systematic review and meta-analysis. Onco Targets Ther, 2016, 9: 1471-1476.
5. 石远凯, 孙燕, 于金明, 等. 中国晚期原发性肺癌诊治专家共识(2016年版). 中国肺癌杂志, 2016, 19(1): 1-15.
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.cochrane-handbook.org..
7. Kim YS, Cho EK, Woo HS, et al. Randomized Phase II Study of Pemetrexed Versus Gefitinib in Previously Treated Patients with Advanced Non-small Cell Lung Cancer. Cancer Res Treat, 2016, 48(1): 80-87.
8. Sun JM, Lee KH, Kim SW, et al. Gefitinib versus pemetrexed as second-line treatment in patients with nonsmall cell lung cancer previously treated with platinum-based chemotherapy (KCSG-LU08-01): an open-label, phase 3 trial. Cancer, 2012, 118(24): 6234-6242.
9. Zhou Q, Cheng Y, Yang JJ, et al. Pemetrexed versus gefitinib as a second-line treatment in advanced nonsquamous nonsmall-cell lung cancer patients harboring wild-type EGFR (CTONG0806): a multicenter randomized trial. Ann Oncol, 2014, 25(12): 2385-2391.
10. 刘孝民. 吉非替尼对比培美曲塞治疗晚期非鳞非小细胞肺癌的临床疗效及安全性评价. 中国临床药理学杂志, 2015, 31(24): 2393-2395.
11. 宋霆婷, 盖慧荣, 李伟, 等. 吉非替尼治疗晚期非小细胞肺癌的疗效观察. 疑难病杂志, 2015, 14(8): 778-781.
12. 张宇卉, 王海宾. 吉非替尼和培美曲塞治疗晚期复发非小细胞肺癌的临床研究. 临床合理用药杂志, 2009, 2(18): 14-16.
13. 张定国, 阮秀丽. 吉非替尼对比培美曲塞二线治疗晚期非小细胞肺癌的临床研究. 癌症进展, 2016, 14(1): 78-80.
14. 张静, 刘素勤, 张洁, 等. 晚期非小细胞肺癌二线治疗不同方案的疗效及成本效益分析. 临床肿瘤学杂志, 2012, 17(10): 908-911.
15. 戴宏宇, 徐玲, 夏春伟, 等. 吉非替尼对比培美曲塞二线治疗晚期非鳞型非小细胞肺癌的随机对照临床研究. 中国肺癌杂志, 2013, 16(8): 405-410.
16. 王美清, 何立香, 彭大为, 等. 培美曲塞与吉非替尼二线治疗晚期NSCLC的对比研究. 中国热带医学, 2012, 12(11): 1361-1363.
17. 赵利红, 汪海岩, 张德芳. 培美曲塞与吉非替尼二线治疗晚期非小细胞肺癌的临床对比分析. 中国肿瘤临床与康复, 2013, 20(11): 1235-1238.
18. Fang JY, Dong HL, Wu KS, et al. Characteristics and Prediction of Lung Cancer Mortality in China from 1991 to 2013. Asian Pac J Cancer Prev, 2015, 16(14): 5829-5834.
19. Qin HF, Qu LL, Liu H, et al. Serum CEA level change and its significance before and after Gefitinib therapy on patients with advanced non-small cell lung cancer. Asian Pac J Cancer Prev, 2013, 14(7): 4205-4208.
20. 周欣, 李晓琴, 王秀丽, 等. 吉非替尼获得性耐药的非小细胞肺癌患者临床特点. 中国癌症杂志, 2015, 25(3): 222-230.
21. 谢亚琳, 梁继珍, 苏宁. 吉非替尼与厄洛替尼在EGFR基因敏感突变晚期NSCLC患者一线治疗中的疗效比较. 南方医科大学学报, 2015, 35(3): 446-449.
22. Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol, 2011, 29(21): 2866-2874.
23. Rosell R, Moran T, Queralt C, et al. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med, 2009, 361(10): 958-967.
24. Kawano Y, Ohyanagi F, Yanagitani N, et al. Pemetrexed and cisplatin for advanced non-squamous non-small cell lung cancer in Japanese patients: phase II study. Anticancer Res, 2013, 33(8): 3327-3333.
25. Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol, 2004, 22(9): 1589-1597.
26. Kim ES, Hirsh V, Mok T, et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet, 2008, 372(9652): 1809-1818.
27. 顾亮, 赵恬, 钦光跃. 吉非替尼对比培美曲塞二线治疗晚期非小细胞肺癌的临床研究. 中国临床药理学与治疗学, 2012, 17(5): 569-573.

Chinese Journal of Evidence-Based Medicine

Gefitinib versus Pemetrexed as Second-line Treatment for Advanced Non-small Cell Lung Cancer: A Meta-analysis

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