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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Gefitinib provides similar effectiveness and improved safety than erlotinib for east Asian populations with advanced non–small cell lung cancer: a meta-analysis

Authors: Wenxiong Zhang, Yiping Wei, Dongliang Yu, Jianjun Xu, Jinhua Peng

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

The first-generation epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib have both been proven effective for treating advanced non–small cell lung cancer (NSCLC), especially in East Asian patients. We conducted this meta-analysis to compare their efficacy and safety in treating advanced NSCLC in this population.

Methods

We systematically searched PubMed, ScienceDirect, The Cochrane Library, Scopus, Ovid MEDLINE, Embase, Web of Science, and Google Scholar for the relevant studies. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse effects (AEs) were analyzed as primary endpoints.

Results

We identified 5829 articles, among which 31 were included in the final analysis. Both gefitinib and erlotinib were effective for treating advanced NSCLC, with comparable PFS (95% confidence interval [CI]: 0.97–1.10, p = 0.26), OS (95% CI: 0.89–1.21, p = 0.61), ORR (95% CI: 1.00–1.18, p = 0.06), and DCR (95% CI: 0.93–1.05, p = 0.68). Erlotinib induced a significantly higher rate of dose reduction (95% CI: 0.13–0.65, p = 0.002) and grade 3–5 AEs (95% CI: 0.27–0.71, p = 0.0008). In subgroup analysis of AEs, the erlotinib group had a significantly higher rate and severity of skin rash, nausea/vomiting, diarrhea, fatigue and stomatitis.

Conclusions

With equal anti-tumor efficacy and fewer AEs compared with erlotinib, gefitinib is more suitable for treating advanced NSCLC in East Asian patients. Further large-scale, well-designed randomized controlled trials are warranted to confirm our findings.
Appendix
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Literature
1.
2.
Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.CrossRefPubMed
3.
Liu TC, Jin X, Wang Y, Wang K. Role of epidermal growth factor receptor in lung cancer and targeted therapies. Am J Cancer Res. 2017;7(2):187–202.PubMedPubMedCentral
4.
Malik PS, Jain D, Kumar L. Epidermal growth factor receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer. Oncology. 2016;91(1):26–34.CrossRefPubMed
5.
6.
7.
Dearden S, Stevens J, Wu YL, Blowers D. Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap). Ann Oncol. 2013;24(9):2371–6.CrossRefPubMedPubMedCentral
8.
Wu YL, Saijo N, Thongprasert S, Yang JC, Han B, Margono B, et al. Efficacy according to blind independent central review: post-hoc analyses from the phase III, randomized, multicenter, IPASS study of first-line gefitinib versus carboplatin/paclitaxel in Asian patients with EGFR mutation-positive advanced NSCLC. Lung Cancer. 2017;104:119–25.CrossRefPubMed
9.
Chang GC, Tsai CM, Chen KC, Yu CJ, Shih JY, Yang TY, et al. Predictive factors of gefitinib antitumor activity in east Asian advanced non-small cell lung cancer patients. J Thorac Oncol. 2006;1(6):520–5.CrossRefPubMed
10.
Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, et al. Randomized phase III study comparing gefitinib with erlotinib in patients with previously treated advanced lung adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016;34(27):3248–57.CrossRefPubMed
11.
Yang JJ, Zhou Q, Yan HH, Zhang XC, Chen HJ, Tu HY, et al. A phase III randomised controlled trial of erlotinib vs gefitinib in advanced non-small cell lung cancer with EGFR mutations. Br J Cancer. 2017;116(5):568–74.CrossRefPubMedPubMedCentral
12.
Shin HJ, Kim TO, Kang HW, Chi SY, Ban HJ, Kim SO, et al. Comparison of therapeutic efficacy of gefitinib and erlotinib in patients with squamous cell lung cancer. Tuberculosis & Respiratory Diseases. 2011;71(1):15–23.CrossRef
13.
Sato S, Kurishima K, Miyazaki K, Kodama T, Ishikawa H, Kagohashi K, et al. Efficacy of tyrosine kinase inhibitors in non-small-cell lung cancer patients undergoing dose reduction and those with a low body surface area. Mol Clin Oncol. 2014;2(4):604–8.CrossRefPubMedPubMedCentral
14.
Fan WC, Yu CJ, Tsai CM, Huang MS, Lai CL, Hsia TC, et al. Different efficacies of erlotinib and gefitinib in taiwanese patients with advanced non-small cell lung cancer: a retrospective multicenter study. J Thorac Oncol. 2011;6(1):148–55.CrossRefPubMed
15.
Kuan FC, Li SH, Wang CL, Lin MH, Tsai YH, Yang CT. Analysis of progression-free survival of first-line tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring leu858Arg or exon 19 deletions. Oncotarget. 2017;8(1):1343–53.CrossRefPubMed
16.
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1):1–12.CrossRefPubMed
17.
Wells GA, Shea BJ, O'Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle–Ottawa scale (nos) for assessing the quality of non-randomized studies in meta-analysis. Appl Eng Agric. 2014;18(6):727–34.
18.
Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.CrossRefPubMedPubMedCentral
19.
Kim ST, Lee J, Kim JH, Won YW, Sun JM, Yun J, et al. Comparison of gefitinib versus erlotinib in patients with non-small cell lung cancer who failed previous chemotherapy. Cancer. 2010;116(12):3025–33.CrossRefPubMed
20.
Hotta K, Kiura K, Takigawa N, Yoshioka H, Harita S, Kuyama S, et al. Comparison of the incidence and pattern of interstitial lung disease during erlotinib and gefitinib treatment in Japanese patients with non-small cell lung cancer: the Okayama lung Cancer study group experience. J Thorac Oncol. 2010;5(2):179–84.CrossRefPubMed
21.
Hong J, Kyung SY, Lee SP, Park JW, Jung SH, Lee JI, et al. Pemetrexed versus gefitinib versus erlotinib in previously treated patients with non-small cell lung cancer. Korean J Intern Med. 2010;25(3):294–300.CrossRefPubMedPubMedCentral
22.
Wu JY, Wu SG, Yang CH, Chang YL, Chang YC, Hsu YC, et al. Comparison of gefitinib and erlotinib in advanced NSCLC and the effect of EGFR mutations. Lung Cancer. 2011;72(2):205–12.CrossRefPubMed
23.
Togashi Y, Masago K, Fujita S, Hatachi Y, Fukuhara A, Nagai H, et al. Differences in adverse events between 250 mg daily gefitinib and 150 mg daily erlotinib in Japanese patients with non-small cell lung cancer. Lung Cancer. 2011;74(1):98–102.CrossRefPubMed
24.
Jung M, Kim SH, Lee YJ, Hong S, Kang YA, Kim SK, et al. Prognostic and predictive value of CEA and CYFRA 21-1 levels in advanced non-small cell lung cancer patients treated with gefitinib or erlotinib. Exp Ther Med. 2011;2(4):685.CrossRefPubMedPubMedCentral
25.
Wu WS, Chen YM, Tsai CM, Shih JF, Chiu CH, Chou KT, et al. Erlotinib has better efficacy than gefitinib in adenocarcinoma patients without EGFR-activating mutations, but similar efficacy in patients with EGFR-activating mutations. Exp Ther Med. 2012;3(2):207–13.CrossRefPubMed
26.
Kim ST, Uhm JE, Lee J, Sun JM, Sohn I, Kim SW, et al. Randomized phase II study of gefitinib versus erlotinib in patients with advanced non-small cell lung cancer who failed previous chemotherapy. Lung Cancer. 2012;75(1):82–8.CrossRefPubMed
27.
Suzumura T, Kimura T, Kudoh S, Umekawa K, Nagata M, Matsuura K, et al. Reduced CYP2D6 function is associated with gefitinib-induced rash in patients with non-small cell lung cancer. BMC Cancer. 2012;12:568.CrossRefPubMedPubMedCentral
28.
Yoshida T, Yamada K, Azuma K, Kawahara A, Abe H, Hattori S, et al. Comparison of adverse events and efficacy between gefitinib and erlotinib in patients with non-small-cell lung cancer: a retrospective analysis. Med Oncol. 2013;30(1):349.CrossRefPubMed
29.
Shao YY, Shau WY, Lin ZZ, Chen HM, Kuo R, Yang JC, et al. Comparison of gefitinib and erlotinib efficacies as third-line therapy for advanced non-small-cell lung cancer. Eur J Cancer. 2013;49(1):106–14.CrossRefPubMed
30.
Lee E, Keam B, Kim DW, Kim TM, Lee SH, Chung DH, et al. Erlotinib versus gefitinib for control of leptomeningeal carcinomatosis in non-small-cell lung cancer. J Thorac Oncol. 2013;8(8):1069–74.CrossRefPubMed
31.
Yu S, Wang Y, Li J, Hao X, Wang B, Wang Z, et al. Gefitinib versus erlotinib as salvage treatment for lung adenocarcinoma patients who benefited from the initial gefitinib: a retrospective study. Thoracic Cancer. 2013;4(2):109–16.CrossRefPubMed
32.
Lim SH, Lee JY, Sun JM, Ahn JS, Park K, Ahn MJ. Comparison of clinical outcomes following gefitinib and erlotinib treatment in non-small-cell lung cancer patients harboring an epidermal growth factor receptor mutation in either exon 19 or 21. J Thorac Oncol. 2014;9(4):506–11.CrossRefPubMed
33.
Lin GN, Peng JW, Liu PP, Liu DY, Xiao JJ, Chen XQ. Elevated neutrophil-to-lymphocyte ratio predicts poor outcome in patients with advanced non-small-cell lung cancer receiving first-line gefitinib or erlotinib treatment. Asia Pac J Clin Oncol. 2014;110(7):2696–703.
34.
Ren S, Su C, Wang Z, Li J, Fan L, Li B, et al. Epithelial phenotype as a predictive marker for response to EGFR-TKIs in non-small cell lung cancer patients with wild-type EGFR. Int J Cancer. 2014;135(12):2962–71.CrossRefPubMed
35.
Li J, Li X, Ren S, Chen X, Zhang Y, Zhou F, et al. miR-200c overexpression is associated with better efficacy of EGFR-TKIs in non-small cell lung cancer patients with EGFR wild-type. Oncotarget. 2014;5(17):7902–16.PubMedPubMedCentral
36.
Takeda M, Okamoto I, Nakagawa K. Survival outcome assessed according to tumor response and shrinkage pattern in patients with EGFR mutation–positive non–small cell lung cancer treated with geftinib or erlotinib. J Thorac Oncol. 2014;9(2):200–4.CrossRefPubMedPubMedCentral
37.
Otsuka T, Mori M, Yano Y, Uchida J, Nishino K, Kaji R, et al. Effectiveness of tyrosine kinase inhibitors in Japanese patients with non-small cell lung cancer harboring minor epidermal growth factor receptor mutations: results from a multicenter retrospective study (HANSHIN oncology group 0212). Anticancer Res. 2015;35(7):3885–91.PubMed
38.
Song Z, Zhang Y. Efficacy of gefitinib or erlotinib in patients with squamous cell lung cancer. Arch Med Sci. 2015;11(1):164–8.CrossRefPubMed
39.
Koo DH, Kim KP, Choi CM, Lee DH, Lee JC, Lee JS, et al. EGFR-TKI is effective regardless of treatment timing in pulmonary adenocarcinoma with EGFR mutation. Cancer Chemother Pharmacol. 2015;75(1):197–206.CrossRefPubMed
40.
Ruan Y, Jiang J, Guo L, Li Y, Huang H, Shen L, et al. Genetic association of curative and adverse reactions to tyrosine kinase inhibitors in Chinese advanced non-small sell lung cancer patients. Sci Rep. 2016;6:23368.CrossRefPubMedPubMedCentral
41.
Hirano R, Uchino J, Ueno M, Fujita M, Watanabe K. Low-dose epidermal growth factor receptor (EGFR)-tyrosine kinase inhibition of EGFR mutation-positive lung cancer: therapeutic benefits and associations between dosage, efficacy and body surface area. Asian Pac J Cancer Prev. 2016;17(2):785–9.CrossRefPubMed
42.
Suh KJ, Keam B, Kim M, Park YS, Kim TM, Jeon YK, et al. Serum neuron-specific enolase levels predict the efficacy of first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring EGFR mutations. Clin Lung Cancer. 2016;17(4):245–52.CrossRefPubMed
43.
Kashima J, Okuma Y, Miwa M, Hosomi Y. Survival of patients with brain metastases from non-small cell lung cancer harboring EGFR mutations treated with epidermal growth factor receptor tyrosine kinase inhibitors. Med Oncol. 2016;33(11):129.CrossRefPubMed
44.
Yun CH, Boggon TJ, Li Y, Woo MS, Greulich H, Meyerson M, et al. Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell. 2007;11(3):217–27.CrossRefPubMedPubMedCentral
45.
Ling J, Fettner S, Lum BL, Riek M, Rakhit A. Effect of food on the pharmacokinetics of erlotinib, an orally active epidermal growth factor receptor tyrosine-kinase inhibitor, in healthy individuals. Anti-Cancer Drugs. 2008;19(2):209–16.CrossRefPubMed
46.
Cantarini MV, McFarquhar T, Smith RP, Bailey C, Marshall AL. Relative bioavailability and safety profile of gefitinib administered as a tablet or as a dispersion preparation via drink or nasogastric tube: results of a randomized, open-label, three-period crossover study in healthy volunteers. Clin Ther. 2004;26(10):1630–6.CrossRefPubMed
47.
Russo A, Franchina T, Ricciardi GR, Picone A, Ferraro G, Zanghì M, et al. A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): old successes and future perspectives. Oncotarget. 2015;6(29):26814–25.CrossRefPubMedPubMedCentral
48.
Yang SC, Lai WW, Hsiue TR, Su WC, Lin CK, Hwang JS, et al. Health-related quality of life after first-line anti-cancer treatments for advanced non-small cell lung cancer in clinical practice. Qual Life Res. 2016;25(6):1441–9.CrossRefPubMed
49.
Wu YL, Fukuoka M, Mok TS, Saijo N, Thongprasert S, Yang JC, et al. Tumor response and health-related quality of life in clinically selected patients from Asia with advanced non-small-cell lung cancer treated with first-line gefitinib: post hoc analyses from the IPASS study. Lung Cancer. 2013;81(2):280–7.CrossRefPubMed
50.
Baselga J, Rischin D, Ranson M, Calvert H, Raymond E, Kieback DG, et al. Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. J Clin Oncol. 2002;20(21):4292–302.CrossRefPubMed
51.
Hidalgo M, Siu LL, Nemunaitis J, Rizzo J, Hammond LA, Takimoto C, et al. Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. J Clin Oncol. 2001;19(13):3267–79.CrossRefPubMed
52.
Rukazenkov Y, Speake G, Marshall G, Anderton J, Davies BR, Wilkinson RW, et al. Epidermal growth factor receptor tyrosine kinase inhibitors: similar but different? Anti-Cancer Drugs. 2009;20(10):856–66.CrossRefPubMed
53.
Mok T, Wu YL, Au JS, Zhou C, Zhang L, Perng RP, Park K. Efficacy and safety of erlotinib in 1242 east/south-east Asian patients with advanced non-small cell lung cancer. J Thorac Oncol. 2010;5(10):1609–15.CrossRefPubMed
54.
Ando M, Okamoto I, Yamamoto N, Takeda K, Tamura K, Seto T, et al. Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib. J Clin Oncol. 2006;24(16):2549–56.CrossRefPubMed
55.
Yeo WL, Riely GJ, Yeap BY, Lau MW, Warner JL, Bodio K, et al. Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. J Thorac Oncol. 2010;5(7):1048–53.CrossRefPubMedPubMedCentral
56.
Takashima N, Kimura T, Watanabe N, Umemura T, Katsuno S, Arakawa K, et al. Prognosis in patients with non-small cell lung cancer who received erlotinib treatment and subsequent dose reduction due to skin rash. Onkologie. 2012;35(12):747–52.CrossRefPubMed
57.
Satoh H, Inoue A, Kobayashi K, Maemondo M, Oizumi S, Isobe H, et al. Low-dose gefitinib treatment for patients with advanced non-small cell lung cancer harboring sensitive epidermal growth factor receptor mutations. J Thorac Oncol. 2011;6(8):1413–7.CrossRefPubMed
58.
Sim SH, Keam B, Kim DW, Kim TM, Lee SH, Chung DH, et al. The gefitinib dose reduction on survival outcomes in epidermal growth factor receptor mutant non-small cell lung cancer. J Cancer Res Clin Oncol. 2014;140(12):2135–42.CrossRefPubMed
59.
Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, et al. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label. ENSURE study Ann Oncol. 2015;26(9):1883–9.CrossRefPubMed
60.
Fukuoka M, Wu YL, Thongprasert S, Sunpaweravong P, Leong SS, Sriuranpong V, 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):2866–74.CrossRefPubMed
61.
Fiala O, Pesek M, Finek J, Benesova L, Bortlicek Z, Minarik M. Comparison of EGFR-TKI and chemotherapy in the first-line treatment of advanced EGFR mutation-positive NSCLC. Neoplasma. 2013;60(4):425–31.CrossRefPubMed
62.
Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011;12(8):735–42.CrossRefPubMed
63.
Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, 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):239–46.CrossRefPubMed
64.
Kazandjian D, Blumenthal GM, Yuan W, He K, Keegan P, Pazdur R. FDA approval of gefitinib for the treatment of patients with metastatic EGFR mutation-positive non-small cell lung cancer. Clin Cancer Res. 2016;22(6):1307–12.CrossRefPubMed
65.
Metadata
Title
Gefitinib provides similar effectiveness and improved safety than erlotinib for east Asian populations with advanced non–small cell lung cancer: a meta-analysis
Authors
Wenxiong Zhang
Yiping Wei
Dongliang Yu
Jianjun Xu
Jinhua Peng
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4685-y

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