Oncotarget

Research Papers:

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

Feng-Che Kuan, Shih-Hong Li, Chih-Liang Wang, Meng-Hung Lin, Ying-Huang Tsai and Cheng-Ta Yang _

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Oncotarget. 2017; 8:1343-1353. https://doi.org/10.18632/oncotarget.13815

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Abstract

Feng-Che Kuan1,2, Shih-Hong Li3, Chih-Liang Wang3,4, Meng-Hung Lin5, Ying-Huang Tsai6,7, Cheng-Ta Yang3,7

1Department of Hematology and Oncology, Department of Medicine, Chang-Gung Memorial Hospital, Chiayi 61363, Taiwan

2Graduate Institute of Clinical Medical Sciences, Chang-Gung University, Taoyuan 33302, Taiwan

3Department of Thoracic Medicine, Chang-Gung Memorial Hospital, Taoyuan 33305, Taiwan

4Department of Medicine, Chang-Gung University, Taoyuan 33302, Taiwan

5Cencer of Excellence for Chang Gung Research Datalink, Chang-Gung Memorial Hospital, Chiayi 61363, Taiwan

6Division of Respiratory and Critical Care Medicine, Department of Medicine, Chang-Gung Memorial Hospital, Chiayi 61363, Taiwan

7Department of Respiratory Therapy, Chang-Gung University, Taoyuan 33302, Taiwan

Correspondence to:

Cheng-Ta Yang, email: [email protected]

Keywords: gefitinib, erlotinib, afatinib, Leu858Arg, Thr790Met

Received: August 15, 2016     Accepted: November 14, 2016     Published: December 07, 2016

ABSTRACT

Background: Gefitinib, erlotinib and afatinib provide remarkable response rates and progression-free survival compared to platinum-based chemotherapy in patients with non-small cell lung cancer harboring epidermal growth factor receptor-activating mutations, and are therefore standard first-line treatment in these patients. However, no study has compared these drugs regarding progression-free survival.

Materials and Methods: We conducted this retrospective study at a single medical center in Taiwan from February 16, 2011 to October 30, 2015. We used the Kaplan-Meier method to estimate survival, and multivariate Cox proportional hazard models to estimate adjusted hazard ratios and 95% confidence intervals.

Findings: Of the 1006 patients diagnosed with stage IIIb and IV non-small cell lung cancer in the study period, 448 (44.5%) had EGFR-activating mutations and received first-line therapy with gefitinib (n = 304, 67.6%), erlotinib (n = 63, 14.3%), or afatinib (n = 81, 18.1%). The median duration of follow-up for progression-free survival was 12.1 months in the gefitinib arm (Interquartile range [IQR]: 5.5–16.5), 11.2 months in the erlotinib arm (IQR: 4.9–16.7), and 10.3 months in the afatinib arm (IQR: 7.0–14.2). Progression-free survival was significantly longer in the patients who received afatinib or erlotinib compared to those who received gefitinib (log-rank test, p < 0.001), and the median progression-free survival was 11.4 months in the gefitinib group.

Interpretation: Afatinib and erlotinib provide significant benefits in progression-free survival compared to gefitinib in first-line treatment of patients with non-small-cell lung cancers harboring EGFR-activating mutations. Further clinical trials are warranted to validate these findings.


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