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：

Export PDF Favorites Scan Get Citation

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.	石遠凱, 孫燕, 于金明, 等. 中國晚期原發性肺癌診治專家共識(2016年版). 中國肺癌雜志, 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.	劉孝民. 吉非替尼對比培美曲塞治療晚期非鱗非小細胞肺癌的臨床療效及安全性評價. 中國臨床藥理學雜志, 2015, 31(24): 2393-2395.
11.	宋霆婷, 蓋慧榮, 李偉, 等. 吉非替尼治療晚期非小細胞肺癌的療效觀察. 疑難病雜志, 2015, 14(8): 778-781.
12.	張宇卉, 王海賓. 吉非替尼和培美曲塞治療晚期復發非小細胞肺癌的臨床研究. 臨床合理用藥雜志, 2009, 2(18): 14-16.
13.	張定國, 阮秀麗. 吉非替尼對比培美曲塞二線治療晚期非小細胞肺癌的臨床研究. 癌癥進展, 2016, 14(1): 78-80.
14.	張靜, 劉素勤, 張潔, 等. 晚期非小細胞肺癌二線治療不同方案的療效及成本效益分析. 臨床腫瘤學雜志, 2012, 17(10): 908-911.
15.	戴宏宇, 徐玲, 夏春偉, 等. 吉非替尼對比培美曲塞二線治療晚期非鱗型非小細胞肺癌的隨機對照臨床研究. 中國肺癌雜志, 2013, 16(8): 405-410.
16.	王美清, 何立香, 彭大為, 等. 培美曲塞與吉非替尼二線治療晚期NSCLC的對比研究. 中國熱帶醫學, 2012, 12(11): 1361-1363.
17.	趙利紅, 汪海巖, 張德芳. 培美曲塞與吉非替尼二線治療晚期非小細胞肺癌的臨床對比分析. 中國腫瘤臨床與康復, 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, 李曉琴, 王秀麗, 等. 吉非替尼獲得性耐藥的非小細胞肺癌患者臨床特點. 中國癌癥雜志, 2015, 25(3): 222-230.
21.	謝亞琳, 梁繼珍, 蘇寧. 吉非替尼與厄洛替尼在EGFR基因敏感突變晚期NSCLC患者一線治療中的療效比較. 南方醫科大學學報, 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.	顧亮, 趙恬, 欽光躍. 吉非替尼對比培美曲塞二線治療晚期非小細胞肺癌的臨床研究. 中國臨床藥理學與治療學, 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. 石遠凱, 孫燕, 于金明, 等. 中國晚期原發性肺癌診治專家共識(2016年版). 中國肺癌雜志, 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. 劉孝民. 吉非替尼對比培美曲塞治療晚期非鱗非小細胞肺癌的臨床療效及安全性評價. 中國臨床藥理學雜志, 2015, 31(24): 2393-2395.
11. 宋霆婷, 蓋慧榮, 李偉, 等. 吉非替尼治療晚期非小細胞肺癌的療效觀察. 疑難病雜志, 2015, 14(8): 778-781.
12. 張宇卉, 王海賓. 吉非替尼和培美曲塞治療晚期復發非小細胞肺癌的臨床研究. 臨床合理用藥雜志, 2009, 2(18): 14-16.
13. 張定國, 阮秀麗. 吉非替尼對比培美曲塞二線治療晚期非小細胞肺癌的臨床研究. 癌癥進展, 2016, 14(1): 78-80.
14. 張靜, 劉素勤, 張潔, 等. 晚期非小細胞肺癌二線治療不同方案的療效及成本效益分析. 臨床腫瘤學雜志, 2012, 17(10): 908-911.
15. 戴宏宇, 徐玲, 夏春偉, 等. 吉非替尼對比培美曲塞二線治療晚期非鱗型非小細胞肺癌的隨機對照臨床研究. 中國肺癌雜志, 2013, 16(8): 405-410.
16. 王美清, 何立香, 彭大為, 等. 培美曲塞與吉非替尼二線治療晚期NSCLC的對比研究. 中國熱帶醫學, 2012, 12(11): 1361-1363.
17. 趙利紅, 汪海巖, 張德芳. 培美曲塞與吉非替尼二線治療晚期非小細胞肺癌的臨床對比分析. 中國腫瘤臨床與康復, 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, 李曉琴, 王秀麗, 等. 吉非替尼獲得性耐藥的非小細胞肺癌患者臨床特點. 中國癌癥雜志, 2015, 25(3): 222-230.
21. 謝亞琳, 梁繼珍, 蘇寧. 吉非替尼與厄洛替尼在EGFR基因敏感突變晚期NSCLC患者一線治療中的療效比較. 南方醫科大學學報, 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. 顧亮, 趙恬, 欽光躍. 吉非替尼對比培美曲塞二線治療晚期非小細胞肺癌的臨床研究. 中國臨床藥理學與治療學, 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

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content