Efficacy and Safety of EGFR-TKIs versus Chemotherapy as the First Line Treatment for Patients with Advanced Non-small Cell Lung Cancer: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

 LIXiang-lian ^1,2 , TANGXue-li ¹ ,  LIYou-ping ¹ , LICui-cui ³ , ZHANGXiao-hong ⁴

1. Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China;
2. Chengdu Military General Hospital, Chengdu 610083, China;
3. Nuclear Industry 416th Hospital, Chengdu 610051, China;
4. Respiration Department, the Sixth People's Hospital of Chengdu, Chengdu 610051, China;

Corresponding author：

LIYou-ping, Email: yzmylab@hotmail.com

Keywords：

Non-small cell lung cancer; EGFR-TKI; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20160031

Video：

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Objective To systematically evaluate the efficacy and safety of epidermal growth factor receptortyrosine kinase inhibitors (EGFR-TKIs) as the first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). Method Databases including PubMed, EMbase, The Cochrane Library (Issue 1, 2015) , CBM, CNKI, VIP and WanFang Data were electronically searched from inception to March 2015, to collect randomized controlled trials (RCTs) about EGFR-TKIs versus chemotherapy for advanced NSCLC patients. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then, meta-analysis was performed by RevMan 5.2 software. Results A total of 9 RCTs involving 3 841 patients were included. The results of meta-analysis showed that: for patients with EGFR mutation-positive, the rate of progression-free survival (PFS) (HR=0.41, 95%CI 0.31 to 0.54, P<0.000 01) , objective response rate (ORR) (RR=2.23, 95% CI 1.73 to 2.87, P<0.000 01) and quality of life (QoL) in the EGFR-TKI group were superior to the chemotherapy group; There was no statistical difference between two groups in rate of overall survival (OS) (HR=1.04, 95% CI 0.88 to 1.24, P=0.62) . The incidences of diarrhea (RR=3.81, 95% CI 2.15 to 6.76, P<0.001) and rash (RR=8.14, 95% CI 3.55 to 18.68, P<0.001) were significantly higher, but the incidence of blood toxicity was lower in the EGFR-TKI group that those in the chemotherapy group. Conclusions Current evidence shows EGFR-TKI is superior to chemotherapy for advanced NSCLC patients with EGFR mutation-positive. However, due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.

Citation： LIXiang-lian, TANGXue-li, LIYou-ping, LICui-cui, ZHANGXiao-hong. Efficacy and Safety of EGFR-TKIs versus Chemotherapy as the First Line Treatment for Patients with Advanced Non-small Cell Lung Cancer: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2016, 16(2): 191-199. doi: 10.7507/1672-2531.20160031 Copy

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17.	Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatinpaclitaxel in pulmonary adenocarcinoma. N Engl J Med, 2009, 361(10) :947-957.
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28.	Lilenbaum R, Axelrod R, Thomas S, et al. Randomized phase II trial of erlotinib or standard chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2. J Clin Oncol, 2008, 26(6) :863-869.
29.	Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol, 2013, 31(27) : 3327-3334.
30.	Yang JC, Hirsh V, Schuler M, et al. Symptom control and quality of life in LUX-Lung 3:a phase III study of afatinib or cisplatin/ pemetrexed in patientswith advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol, 2013, 31(27) :3342-3350.
31.	Estimated cancer Incidence, Mortality, Prevalence and Disabilityadjusted life years (DALYs) world wide in 2012. Available at:http://globocan.iarc.fr/.
32.	Pakkala S, Ramalingam SS. Combined inhibition of vascular endothelial growth factor and epidermal growth factor signaling in non-small cell lung cancer therapy. Clin Lung Cancer, 2009, 10(Suppl 1) :S17-23.
33.	Wu YL, Lee JS, Thongprasert S, et al. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage nonsmall-cell lung cancer (FASTACT-2) :a randomised, double-blind trial. Lancet Oncol, 2013, 14(8) :777-786.
34.	郭珑华,吴一龙,周清.非小细胞肺癌表皮生长因子受体基因突变的异质性. 肿瘤研究与临床, 2012, 24(9) :577-588.

1. Soerjomataram I, Lortet-Tieulent J, Parkin DM, et al. Global burden of cancer in 2008:a systematic analysis of disability-adjusted lifeyears in 12 world regions. Lancet, 2012, 380(9856) :1840-1850.
2. Berghmans T, Pasleau F, Paesmans M, et al. Surrogate markers predicting overall survival for lung cancer:ELCW P recommendations. Eur Respir J, 2012, 39(1) :9-28.
3. Non-Small Cell Lung Cancer Collaborative Group. Chemotherapyinnon-smallcelllungcancer:ameta-analysisusingupdateddataon individual patients from 52 randomised clinical trials. BMJ, 1995, 311(7010) :899-909.
4. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology-Non-Small Cell Lung Cancer. Available at: http://www.nccn.com.2013.
5. Ihbe-Heffinger A, Paessens B, Berger K, et al. The impact of chemotherapy-induced side effects on medical care usage and cost in German hospital care-an observational analysis on non-smallcell lung cancer patients. Support Care Cancer, 2013, 21(6) :1665-1675.
6. Socinski MA, Evans T, Gettinger S, et al. Treatment of stage IV nonsmall cell lung cancer:Diagnosis and management of lung cancer, 3rd ed:American College of Chest Physicians evidence-based clinical practice guidelines. Chest, 2013, 143(5 Suppl):e341S-368S.
7. NICE. The diagnosis and treatment of lung cancer. 2011. Available at:http://guidance.nice.org.uk/cg121.
8. D'Addario G, Felip E. Non-small-cell lung cancer:ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Ann Oncol, 2009, 20 (Suppl 4) :68-70.
9. De Marinis F, Rossi A, Di MM, et al. Treatment of advanced nonsmall-cell lung cancer:Italian Association of Thoracic Oncology (AIOT) clinical practice guidelines. Lung Cancer, 2011, 73(1) :1-10.
10. Sharma SV, Bell DW, Settleman J, et al. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer, 2007, 7:169-181.
11. Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Available at:http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf.
12. Cochrane Handbook for Systematic Reviews of Interventions 5.2. The Cochrane Collaboration, 2009.
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. Oizumi S, Kobayashi K, Inoue A, et al. Quality of life with gefitinib in patients with EGFR-mutated non-small cell lung cancer: quality of life analysis of North East Japan Study Group 002 Trial. Oncologist, 2012, 17(6) :863-870.
15. 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-naive non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002) . Ann Oncol, 2013, 24(1) :54-59.
16. 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, 2013, 11(2) :121-128.
17. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatinpaclitaxel in pulmonary adenocarcinoma. N Engl J Med, 2009, 361(10) :947-957.
18. Thongprasert S, Duffield E, Saijo N, et al. Health-related qualityof-life in a randomized phase III first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients from Asia with advanced NSCLC (IPASS). J Thorac Oncol, 2011, 6(11) :1872-1880.
19. Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase III, randomized, openlabel, 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.
20. Lee Y, Kim SH, Han JY, et al. Early neutrophil-to-lymphocyte ratio reduction as a surrogate marker of prognosis in never smokers with advanced lung adenocarcinoma receiving gefitinib or standard chemotherapy as first-line therapy. J Cancer Res Clin Oncol, 2012,.
21. (12) :2009-2016.
22. Han JY, Park K, Kim SW, et al. First-SIGNAL:First-Line SingleAgent Iressa Versus Gemcitabine and Cisplatin Trial in NeverSmokers With Adenocarcinoma of the Lung. J Clin Oncol, 2012, 30(10) :1122-1128.
23. Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutationpositive non-small-cell lung cancer (OPTIMAL, CTONG-0802) :a multicentre, open-label, randomised, phase 3 study. Lancet Oncol, 2011, 12(8) :735-742.
24. Chen G, Feng J, Zhou C, et al. Quality of lif e (QoL) analyses from OPTIMAL(CTONG-0 802) , a phase III, randomised, open-label study of first-line erlotinib versus chemotherapy in patients with advanced EGFR mutation-positive non-small-cell lung cancer (NSCLC). Ann Oncol, 2013, 24(6) :1615-1622.
25. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC):a multicentre, open-label, randomised phase 3 trial. Lancet Oncol, 2012, 13(3) :239-246.
26. Gridelli C, Rossi A. EURTAC first-line phase III randomized study in advanced non-small cell lung cancer:Erlotinib works also in European population. J Thorac Dis, 2012, 4(2) :219-220.
27. Gridelli C, Ciardiello F,Gallo C, et al. First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced nonsmall-cell lung cancer:the TORCH randomized trial. J Clin Oncol, 2012, 30(24) :3002-3011.
28. Lilenbaum R, Axelrod R, Thomas S, et al. Randomized phase II trial of erlotinib or standard chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2. J Clin Oncol, 2008, 26(6) :863-869.
29. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol, 2013, 31(27) : 3327-3334.
30. Yang JC, Hirsh V, Schuler M, et al. Symptom control and quality of life in LUX-Lung 3:a phase III study of afatinib or cisplatin/ pemetrexed in patientswith advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol, 2013, 31(27) :3342-3350.
31. Estimated cancer Incidence, Mortality, Prevalence and Disabilityadjusted life years (DALYs) world wide in 2012. Available at:http://globocan.iarc.fr/.
32. Pakkala S, Ramalingam SS. Combined inhibition of vascular endothelial growth factor and epidermal growth factor signaling in non-small cell lung cancer therapy. Clin Lung Cancer, 2009, 10(Suppl 1) :S17-23.
33. Wu YL, Lee JS, Thongprasert S, et al. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage nonsmall-cell lung cancer (FASTACT-2) :a randomised, double-blind trial. Lancet Oncol, 2013, 14(8) :777-786.
34. 郭珑华,吴一龙,周清.非小细胞肺癌表皮生长因子受体基因突变的异质性. 肿瘤研究与临床, 2012, 24(9) :577-588.

Chinese Journal of Evidence-Based Medicine

Efficacy and Safety of EGFR-TKIs versus Chemotherapy as the First Line Treatment for Patients with Advanced Non-small Cell Lung Cancer: A Systematic Review

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