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. 2017 Jan 3;8(1):1343-1353.
doi: 10.18632/oncotarget.13815.

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  1   2 , Shih-Hong Li  3 , Chih-Liang Wang  3   4 , Meng-Hung Lin  5 , Ying-Huang Tsai  6   7 , Cheng-Ta Yang  3   7
Affiliations

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 et al. Oncotarget. .

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.

Keywords: Leu858Arg; Thr790Met; afatinib; erlotinib; gefitinib.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare no conflicts of interest, such as employment, consultancies, stock ownership, honoraria, paid expert testimony, and travel grants that may be perceived as prejudicing the impartiality of the research.

Figures

Figure 1
Figure 1. Patient disposition
Figure 2
Figure 2. Kaplan-Meier survival curves of progression-free survival in patients received gefitinib, erlotinib and afatinib
Figure 3
Figure 3. Kaplan-Meier survival curves of progression-free survival in patients received (A) afatinib and gefitinib and (B) erlotinib and gefitinib
Figure 4
Figure 4. Multivariable analysis of progression-free survival in patients received afatinib v.s
gefitinib and erlotinib v.s. gefitinib
Figure 5
Figure 5. Kaplan-Meier survival curves of progression-free survival of patients received gefitinib, erlotinib and afatinib in (A) exon 19 deletions and (B) Leu858Arg
See this image and copyright information in PMC

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