Gefitinib in first-line precision treatment for patients with advanced non-small cell lung cancer: a Meta-analysis_West China Medical Journal

Authors：

HU Qiaozhi ^1,2 , ZHAN Mei ¹ , WU Bin ¹ , TIAN Fangyuan ^1,2 ,  XU Ting ¹

1. Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

XU Ting, Email: tingx2009@163.com

Keywords：

Gefitinib; Platinum-based doublets chemotherapy; Non-small cell lung cancer; Systematic review; Meta-analysis

DOI：

10.7507/1002-0179.201604228

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Objective To evaluate the safety and efficacy of gefitinib in comparison with platinum-based doublets chemotherapy as a first-line precision treatment for advanced non-small cell lung cancer (NSCLC), and find the benefit population of gefitinib. Methods The Cochrane Library, PubMed, Embase, China National Knowledge Internet, VIP database and China Biology Medicine database were searched to collect the randomized contolled trials (RCTs) of gefitinib vs. platinum-based doublets chemotherapy for advanced NSCLC from inception to November, 2017. The data in the included RCTs were extracted, and the qualities were assessed in accordance with Cochrane Collaboration, and a Meta-analysis was conducted with RevMan 5.3 software. Results Four trials were included, including 968 subjects in the gefitinib group and 968 subjects in the chemotherapy group, and a majority of the subjects were diagnosed advanced adenocarcinoma, and all of the subjects were East Asians. The results of Meta-analysis showed that in all population or patients with epidermal growth factor receptor (EGFR) mutation-positive, gefitinib was better than chemotherapy in progression-free survival (PFS) [in all population: hazard ratio (HR)=0.76, 95% confidence interval (CI) (0.67, 0.85), P<0.000 01; in patients withEGFR mutation-positive: HR=0.42, 95%CI (0.35, 0.50), P<0.000 01] and objective response rate (ORR) [in all population: risk ratio (RR)=1.30, 95%CI (1.15, 1.47), P<0.000 1; in patients withEGFR mutation-positive: RR=1.92, 95%CI (1.46, 2.52), P<0.000 01], and there was no significant difference between the two groups in overall survival (OS) (P>0.05); but inEGFR mutation-negative, chemotherapy was better than gefitinib in PFS [HR=2.09, 95%CI (1.05, 4.13), P=0.03]. Subgroup analysis showed that in female patients, for patients with Performance Status (PS) score 0 or 1, and the ones who never smoked, gefitinib was better than chemotherapy in PFS (P<0.05); but there was no significant difference between the two groups in OS (P>0.05). The incidences of rash, itching, dry skin, paronychia, diarrhea, aminotransferase abnormality were higher in the gefitinib group (P<0.05), while the incidences of hair loss, vomiting, nausea, constipation, anorexia, leukopenia, thrombocytopenia, and neutropenia, anemia, fatigue, nerve toxicity reaction were higher in the chemotherapy group (P<0.05). Conclutions Based on the current evidence, in patients with adenocarcinoma of East Asians, the benefit population are those with the characteristics of EGFR mutation-positive, female, never smoking, and PS 0 or 1. In the aspect of safety, the common adverse drug events in subjects treated with gefitinib are the damage of skin mucous membrane, but the incidences of digestive system diseases and the blood system diseases are less in patients treated with gefitinib than those with chemotherapy.

Citation： HU Qiaozhi, ZHAN Mei, WU Bin, TIAN Fangyuan, XU Ting. Gefitinib in first-line precision treatment for patients with advanced non-small cell lung cancer: a Meta-analysis. West China Medical Journal, 2018, 33(1): 60-66. doi: 10.7507/1002-0179.201604228 Copy

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2.	韩忠辉. 医院 2005-2009 年恶性肿瘤住院病例统计分析. 现代医药卫生, 2011, 27(7): 1017-1018.
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7.	Miller VA, Kris MG, Shah N, et al. Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. J Clin Oncol, 2004, 22(6): 1103-1109.
8.	Comis RL. The current situation: erlotinib (Tarceva) and gefitinib (Iressa) in non-small cell lung cancer. Oncologist, 2005, 10(7): 467-470.
9.	Arteaga CL. Selecting the right patient for tumor therapy. Nat Med, 2004, 10(6): 577-578.
10.	Wu YL, Zhong WZ, Li LY, et al. Epidermal growth factor receptor mutations and their correlation with gefitinib therapy in patients with non-small cell lung cancer: a meta-analysis based on updated individual patient data from six medical centers in mainland China. J Thorac Oncol, 2007, 2(5): 430-439.
11.	Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. www.cochranehandbook.org.
12.	Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol, 2010, 11(2): 121-128.
13.	Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR N Engl J Med, 2010, 362(25): 2380-2388.
14.	Inoue A, Kobayashi K, Maemondo M, et al. Updated overall survival results from a randomized phase Ⅲ trial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002) Ann Oncol, 2013, 24(1): 54-59.
15.	Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med, 2009, 361(10): 947-957.
16.	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.
17.	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.
18.	National Research Council. Toward precision medicine: building a knowledge network for biomedical research and a new taxonomy of disease. Washington, DC: The National Academies Press, 2011. https://doi.org/10.17226/13284.

1. Zheng R, Zeng H, Zuo T, et al. Lung cancer incidence and mortality in China, 2011. Thoracic Cancer, 2016, 7(1): 94-99.
2. 韩忠辉. 医院 2005-2009 年恶性肿瘤住院病例统计分析. 现代医药卫生, 2011, 27(7): 1017-1018.
3. Ettinger DS, Wood DE, Akerley W, et al. Non-small cell lung cancer, version 6.2015. J Natl Compr Canc Netw, 2015, 13(5): 515-524.
4. 中华医学会呼吸病学分会肺癌学组. 中国肺癌防治联盟.晚期非小细胞肺癌分子靶向治疗专家共识(2013 版). 中华结核和呼吸杂志, 2014, 37(3): 177-183.
5. Paez JG, Jänne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science, 2004, 304(5676): 1497-1500.
6. Kim KS, Jeong JY, Kim YC, et al. Predictors of the response to gefitinib in refractory non-small cell lung cancer. Clin Cancer Res, 2005, 11(6): 2244-2251.
7. Miller VA, Kris MG, Shah N, et al. Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer. J Clin Oncol, 2004, 22(6): 1103-1109.
8. Comis RL. The current situation: erlotinib (Tarceva) and gefitinib (Iressa) in non-small cell lung cancer. Oncologist, 2005, 10(7): 467-470.
9. Arteaga CL. Selecting the right patient for tumor therapy. Nat Med, 2004, 10(6): 577-578.
10. Wu YL, Zhong WZ, Li LY, et al. Epidermal growth factor receptor mutations and their correlation with gefitinib therapy in patients with non-small cell lung cancer: a meta-analysis based on updated individual patient data from six medical centers in mainland China. J Thorac Oncol, 2007, 2(5): 430-439.
11. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. www.cochranehandbook.org.
12. Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol, 2010, 11(2): 121-128.
13. Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR N Engl J Med, 2010, 362(25): 2380-2388.
14. Inoue A, Kobayashi K, Maemondo M, et al. Updated overall survival results from a randomized phase Ⅲ trial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002) Ann Oncol, 2013, 24(1): 54-59.
15. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med, 2009, 361(10): 947-957.
16. 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.
17. 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.
18. National Research Council. Toward precision medicine: building a knowledge network for biomedical research and a new taxonomy of disease. Washington, DC: The National Academies Press, 2011. https://doi.org/10.17226/13284.

West China Medical Journal

Gefitinib in first-line precision treatment for patients with advanced non-small cell lung cancer: a Meta-analysis

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