Survival benefit of first-generation epidermal growth factor receptor–tyrosine kinase inhibitors in female with advanced lung cancer

Abstract

Background:

This study aimed to estimate therapeutic effects of first-generation epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) in real-world practice, by analyzing survival outcomes in an unselected, Korean female population with advanced lung cancer based on the National Health Insurance Service database.

Methods:

We identified women with newly diagnosed advanced lung cancer from January 2004 to December 2013. For progression-free survival (PFS) and overall survival (OS) analyses, patients were defined into the following subgroups: group A, treated with first-generation EGFR-TKI ⩾6 months; group B, treated with EGFR-TKIs <6 months but at least >1 month; and group C, treated with cytotoxic chemotherapy as follows: monotherapy or combination therapy with gemcitabine or pemetrexed; or monotherapy with docetaxel, paclitaxel, or vinorelbine.

Results:

Among 11,045 enrolled patients, 6170 (55.8%) were treated with first-generation EGFR-TKIs for at least 1 month. The median OS for patients treated with EGFR-TKIs was significantly longer than that of EGFR-TKI-naive patients (19.1 months [95% confidence interval (CI) 18.5–19.7] vs 9.5 months [95% CI 9.1–9.8], P<0.001). In subgroup analysis, group A had a significantly longer median OS compared with group B (30.3 months [95% CI 29.5–31.2] vs 12.3 months [95% CI 11.9–12.7], P<0.001). The median PFS of group A was significantly longer than that of group B (15.8 vs 3.7 months, P<0.001).

Conclusions:

Our analysis demonstrates that EGFR-TKIs confer significant PFS and OS benefits in the real-world practice for Korean female with advanced lung cancer.

Keywords

Advanced lung cancer big data EGFR-TKI female Korea

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References

Ferlay

Soerjomataram

Dikshit

et al . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136: E359–386.

Devesa

Bray

Vizcaino

et al . International lung cancer trends by histologic type: male:female differences diminishing and adenocarcinoma rates rising. Int J Cancer 2005; 117: 294–299.

Lortet-Tieulent

Soerjomataram

Ferlay

et al . International trends in lung cancer incidence by histological subtype: adenocarcinoma stabilizing in men but still increasing in women. Lung Cancer 2014; 84: 13–22.

Toh

Gao

Lim

et al . Never-smokers with lung cancer: epidemiologic evidence of a distinct disease entity. J Clin Oncol 2006; 24: 2245–2251.

Goss

Tsai

Shepherd

et al . Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol 2016; 17: 1643–1652.

Mok

Thongprasert

et al . Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947–957.

Schiller

Harrington

Belani

et al . Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346: 92–98.

Rosell

Carcereny

Gervais

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: 239–246.

Maemondo

Inoue

Kobayashi

et al . Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010; 362: 2380–2388.

10.

Zhou

Liam

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: 1883–1889.

11.

Mitsudomi

Morita

Yatabe

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: 121–128.

12.

Midha

Dearden

McCormack

EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res 2015; 5: 2892–2911.

13.

Organization for Economic Cooperation and Development (OECD). Health at a Glance 2015: OECD Indicators, http://dx.doi.org/10.1787/health_glance-2015-en (2015, accessed July 26 2017).

14.

Kim

Cho

et al . Trends in the prevalence of major cardiovascular disease risk factors among Korean adults: results from the Korea National Health and Nutrition Examination Survey, 1998–2012. Int J Cardiol 2014; 174: 64–72.

15.

Jackman

Pao

Riely

et al . Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol 2010; 28: 357–360.

16.

Lee

Ding

et al . Impact of specific epidermal growth factor receptor (EGFR) mutations and clinical characteristics on outcomes after treatment with EGFR tyrosine kinase inhibitors versus chemotherapy in EGFR-mutant lung cancer: a meta-analysis. J Clin Oncol 2015; 33: 1958–1965.

17.

Shi

Thongprasert

et al . A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol 2014; 9: 154–162.

18.

Socinski

Obasaju

Gandara

et al . Clinicopathologic features of advanced squamous NSCLC. J Thorac Oncol 2016; 11: 1411–1422.

19.

Shin

Kim

et al . Lung cancer epidemiology in Korea. Cancer Res Treat 2017; 49: 616–626.

20.

Berardi

Morgese

Santinelli

et al . Hormonal receptors in lung adenocarcinoma: expression and difference in outcome by sex. Oncotarget 2016; 7: 82648–82657.

21.

Jamal

Homa

O’Connor

et al . Current cigarette smoking among adults: United States, 2005–2014. MMWR Morb Mortal Wkly Rep 2015; 64: 1233–1240.

22.

Aspinall

Mitton

Smoking prevalence and the changing risk profiles in the UK ethnic and migrant minority populations: implications for stop smoking services. Public Health 2014; 128: 297–306.

23.

Kim

Cho

et al . Impact of cigarette smoking on response to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in lung adenocarcinoma with activating EGFR mutations. Lung Cancer 2014; 84: 196–202.

24.

Filosto

Becker

Goldkorn

Cigarette smoke induces aberrant EGF receptor activation that mediates lung cancer development and resistance to tyrosine kinase inhibitors. Mol Cancer Ther 2012; 11: 795–804.

25.

Filosto

Baston

Chung

et al . Src mediates cigarette smoke-induced resistance to tyrosine kinase inhibitors in NSCLC cells. Mol Cancer Ther 2013; 12: 1579–1590.

26.

Greenhalgh

Dwan

Boland

et al . First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer. Cochrane Database Syst Rev 2016; 5: CD010383.

27.

Koo

Kim

Choi

et al . EGFR-TKI is effective regardless of treatment timing in pulmonary adenocarcinoma with EGFR mutation. Cancer Chemother Pharmacol 2015; 75: 197–206.

28.

Zhang

Yang

et al . Comparison of outcomes of tyrosine kinase inhibitor in first- or second-line therapy for advanced non-small-cell lung cancer patients with sensitive EGFR mutations. Oncotarget 2016; 7: 68442–68448.

29.

Yang

Schuler

et al . Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 2015; 16: 141–151.

30.

Kazandjian

Blumenthal

Yuan

et al . FDA Approval of gefitinib for the treatment of patients with metastatic EGFR mutation-positive non-small cell lung cancer. Clin Cancer Res 2016; 22: 1307–1312.

31.

Soria

Ohe

Vansteenkiste

et al . Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med 2018; 378: 113–125.

32.

Zhu

Jia

Role of big data in reducing the bias of a cohort study. Chin Med J 2014; 127: 3842–3844.

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