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Published in: Clinical and Experimental Medicine 1/2018

01-02-2018 | Review Article

Are EGFR tyrosine kinase inhibitors effective in elderly patients with EGFR-mutated non-small cell lung cancer?

Authors: Giandomenico Roviello, Laura Zanotti, Maria Rosa Cappelletti, Angela Gobbi, Martina Dester, Giovanni Paganini, Chiara Pacifico, Daniele Generali, Raheleh Roudi

Published in: Clinical and Experimental Medicine | Issue 1/2018

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Abstract

EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib, and afatinib changed dramatically the history of metastatic non-small cell lung cancer (NSCLC) harbouring EGFR mutations. However, not enough data are available on the efficacy of these targeted drugs in elderly patients. The aim of this study is to analyse the available clinical data evaluating the efficacy of anti-EGFR therapies in elderly patients with advanced NSCLC carrying EGFR mutations. A literature-based meta-analysis of the results of randomized clinical trials was undertaken. Relevant publications from PubMed, the Cochrane Library, and abstracts from American Society of Clinical Oncology meetings were searched. Progression-free survival (PFS), as a measure of the efficacy of treatment, was the primary outcome investigated. The pooled analysis revealed an overall significant improvement in PFS (HR = 0.44, 95% CI 0.28–0.69; p = 0.0004) with the use of EGFR TKIs in EGFR-mutated NSCLC. The data stratification per age subgroups showed that EGFR TKIs were more effective in prolonging PFS in elderly patients, with HR 0.39 (p = 0.008), in comparison with young patients (HR = 0.48; p = 0.04). The results of this study suggest that EGFR TKIs have a significant effect in slowing down diseases progression in elderly patients with advanced NSCLC, therefore representing a valid therapeutic option in this age group.
Literature
1.
go back to reference Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRefPubMed Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.CrossRefPubMed
2.
go back to reference Owonikoko TK, Ragin CC, Belani CP, et al. Lung cancer in elderly patients: an analysis of the surveillance, epidemiology, and end results database. J Clin Oncol. 2007;25:5570–7.CrossRefPubMed Owonikoko TK, Ragin CC, Belani CP, et al. Lung cancer in elderly patients: an analysis of the surveillance, epidemiology, and end results database. J Clin Oncol. 2007;25:5570–7.CrossRefPubMed
3.
go back to reference Reis LAG, Eisner MP, Kosary CL, et al. SEER cancer statistics review, 1975–2002. Bethesda: National Cancer Institute; 2005. p. 6. Reis LAG, Eisner MP, Kosary CL, et al. SEER cancer statistics review, 1975–2002. Bethesda: National Cancer Institute; 2005. p. 6.
4.
go back to reference 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;362:2380–8.CrossRefPubMed 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;362:2380–8.CrossRefPubMed
5.
go back to reference 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;11:121–8.CrossRefPubMed 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;11:121–8.CrossRefPubMed
6.
go back to reference 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;29:2866–74.CrossRefPubMed 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;29:2866–74.CrossRefPubMed
7.
go back to reference Zhou C, Wu YL, Chen G, 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;12:735–42.CrossRefPubMed Zhou C, Wu YL, Chen G, 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;12:735–42.CrossRefPubMed
8.
go back to reference 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;30:1122–8.CrossRefPubMed 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;30:1122–8.CrossRefPubMed
9.
go back to reference 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;13:239–46.CrossRefPubMed 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;13:239–46.CrossRefPubMed
10.
go back to reference 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;31:3327–34.CrossRefPubMed 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;31:3327–34.CrossRefPubMed
11.
go back to reference Wu YL, Zhou C, Hu CP, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15:213–22.CrossRefPubMed Wu YL, Zhou C, Hu CP, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15:213–22.CrossRefPubMed
12.
go back to reference Wu YL, Zhou C, Liam CK, 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;26:1883–9.CrossRefPubMed Wu YL, Zhou C, Liam CK, 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;26:1883–9.CrossRefPubMed
13.
go back to reference Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the prisma statement. PLoS Med. 2009;6:e1000097.CrossRefPubMedPubMedCentral Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the prisma statement. PLoS Med. 2009;6:e1000097.CrossRefPubMedPubMedCentral
14.
go back to reference Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.CrossRefPubMed Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.CrossRefPubMed
15.
16.
go back to reference Cochran WG. The combination of estimates from different experiments. Biometrics. 1954;10:101–29.CrossRef Cochran WG. The combination of estimates from different experiments. Biometrics. 1954;10:101–29.CrossRef
18.
go back to reference Urata Y, Katakami N, Morita S, et al. Randomized phase III study comparing gefitinib with erlotinib in patients with previously treated advanced lung adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016;34:3248–57.CrossRefPubMed Urata Y, Katakami N, Morita S, et al. Randomized phase III study comparing gefitinib with erlotinib in patients with previously treated advanced lung adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016;34:3248–57.CrossRefPubMed
19.
go back to reference Park K, Tan EH, O’Byrne K, et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016;17:577–89.CrossRefPubMed Park K, Tan EH, O’Byrne K, et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016;17:577–89.CrossRefPubMed
20.
go back to reference Wingo PA, Cardinez CJ, Landis SH, et al. Long-term trends in cancer mortality in the United States, 1930–1998. Cancer. 2003;97:3133–275.CrossRefPubMed Wingo PA, Cardinez CJ, Landis SH, et al. Long-term trends in cancer mortality in the United States, 1930–1998. Cancer. 2003;97:3133–275.CrossRefPubMed
22.
go back to reference Rowe J, Patel S, Mazo-Canola M, et al. An evaluation of elderly patients (≥70 years old) enrolled in Phase I clinical trials at University of Texas Health Science Center at San Antonio-Cancer Therapy Research Center from 2009 to 2011. J Geriatr Oncol. 2014;5:65–70.CrossRefPubMed Rowe J, Patel S, Mazo-Canola M, et al. An evaluation of elderly patients (≥70 years old) enrolled in Phase I clinical trials at University of Texas Health Science Center at San Antonio-Cancer Therapy Research Center from 2009 to 2011. J Geriatr Oncol. 2014;5:65–70.CrossRefPubMed
24.
go back to reference Des Guetz G, Landre T, Westeel V, et al. Similar survival rates with first-line gefitinib, gemcitabine, or docetaxel in a randomized phase II trial in elderly patients with advanced non-small cell lung cancer and a poor performance status (IFCT-0301). J Geriatr Oncol. 2015;6:233–40.CrossRefPubMed Des Guetz G, Landre T, Westeel V, et al. Similar survival rates with first-line gefitinib, gemcitabine, or docetaxel in a randomized phase II trial in elderly patients with advanced non-small cell lung cancer and a poor performance status (IFCT-0301). J Geriatr Oncol. 2015;6:233–40.CrossRefPubMed
Metadata
Title
Are EGFR tyrosine kinase inhibitors effective in elderly patients with EGFR-mutated non-small cell lung cancer?
Authors
Giandomenico Roviello
Laura Zanotti
Maria Rosa Cappelletti
Angela Gobbi
Martina Dester
Giovanni Paganini
Chiara Pacifico
Daniele Generali
Raheleh Roudi
Publication date
01-02-2018
Publisher
Springer International Publishing
Published in
Clinical and Experimental Medicine / Issue 1/2018
Print ISSN: 1591-8890
Electronic ISSN: 1591-9528
DOI
https://doi.org/10.1007/s10238-017-0460-7

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