Abstract
BackgroundGefitinib, 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 MethodsWe 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.FindingsOf 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.InterpretationAfatinib 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.
Highlights
Targeting epidermal growth factor receptor (EGFR) and downstream signaling transduction has been shown to be beneficial in the treatment of lung cancer, which accounts for 19.4% of all cancer-related deaths worldwide [1, 2]
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 standard first-line treatment in these patients
Afatinib (Giotrif®, marketed by Boehringer Ingelheim), a secondgeneration EGFR tyrosine kinase inhibitor, unlike gefitinib and erlotinib, provides irreversible inhibition of adenosine triphosphate (ATP) binding by forming permanent covalent bonds, and it has been shown to be active in preclinical study against mutations such as Thr790Met [6], which have been shown to contribute to primary and acquired resistance to reversible tyrosine kinase inhibitors [7,8,9]
Summary
Targeting epidermal growth factor receptor (EGFR) and downstream signaling transduction has been shown to be beneficial in the treatment of lung cancer, which accounts for 19.4% of all cancer-related deaths worldwide [1, 2]. De novo Thr790Met is more likely to coexist with Leu858Arg than with exon 19 deletions, and these two mutations account for around 90% of EGFR-activating mutations [10, 11] All of these tyrosine kinase inhibitors have shown remarkable response rates and benefits in progression-free survival compared to first-line conventional platinumbased chemotherapy [12,13,14,15,16,17,18,19,20,21], and they have become the standard treatment for patients with metastatic nonsmall-cell lung cancer harboring EGFR-activating mutations [22]. 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 standard first-line treatment in these patients. No study has compared these drugs regarding progression-free survival
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