Abstract
ObjectivesLarge-scale, population-based real-world studies on the treatment outcomes of first-line tyrosine kinase inhibitors (TKIs) and subsequent systemic chemotherapy agents for lung adenocarcinoma (with activating epidermal growth factor receptor [EGFR] mutations) remain limited.Materials and MethodsFrom March 2014 to December 2016, patients with advanced lung adenocarcinoma, identified from the Taiwan Cancer Registry were included in this study if they received any of the three TKIs as first-line treatment. The primary outcome was overall survival (OS). The secondary outcome was time-to-treatment discontinuation (TTD).ResultsA total of 4,889 patients (median age: 67 years and two-thirds with distant metastasis) were recruited (1,778 gefitinib, 1,599 erlotinib, and 1,512 afatinib users). A 1:1 propensity score (PS)-matched cohorts of 1,228 afatinib/erlotinib and 1054 afatinib/gefitinib was created. After PS matching, it was found that afatinib was not associated with better OS (afatinib vs. erlotinib, HR: 0.96, 95% CI: 0.86–1.07; afatinib vs. gefitinib, HR: 0.91, 95% CI: 0.81–1.02). In the subgroup analysis, afatinib demonstrated a survival benefit in patients with active smoking (afatinib vs. erlotinib, HR: 0.69, 95% CI: 0.51–0.93; afatinib vs. gefitinib, HR: 0.67, 95% CI: 0.48–0.94) and ECOG > 1 (afatinib vs. erlotinib, HR: 0.79, 95% CI: 0.63–0.99; afatinib vs. gefitinib, HR: 0.78, 95% CI: 0.62–0.98). A total of 41.1% (n = 1992) of first-line TKI users received subsequent chemotherapy. Among the three TKI groups, pemetrexed usage was associated with better OS compared with other chemotherapy agents, with the exception of gemcitabine in the afatinib and gefitinib groups. Pemetrexed and gemcitabine had the longest TTD of 3–4 months.ConclusionsAmong patients with EGFR mutant lung adenocarcinoma, afatinib use may not provide longer OS compared with first-generation TKIs. Afatinib may be preferably considered among patients with active smoking and should not be withheld among those with worse performance status. With 40% of patients receiving subsequent chemotherapy, pemetrexed may be the preferred agent, while gemcitabine can be a reasonable alternative.
Highlights
Lung cancer is the leading cause of cancer-related deaths in the 21st century [1, 2]
Between May 2014 and December 2016, a total of 4,889 advanced lung adenocarcinoma patients with the epidermal growth factor receptor (EGFR) mutation receiving tyrosine kinase inhibitor (TKI) as first-line therapy were included in our study (Figure 1)
Comparing the overall survival (OS) of different second-line chemotherapy regimens, pemetrexed was associated with better OS than was vinorelbine in gefitinib users with advanced EGFR mutant lung adenocarcinoma
Summary
Lung cancer is the leading cause of cancer-related deaths in the 21st century [1, 2]. Multiple generations of EGFR tyrosine kinase inhibitors (TKIs) have been effective as first-line therapy for advanced EGFRmutant lung adenocarcinoma patients [8,9,10,11,12]. All of them provide robust and similar effects in advanced EGFR-mutant lung adenocarcinoma patients [11, 13, 14]. Several real-world studies have investigated the characteristics and clinical effectiveness of these three EGFR TKIs administered in advanced lung adenocarcinoma patients [16,17,18,19,20]. The conclusions from these studies may not provide convincing evidence for clinical practice because of their limited case numbers, discrepant recruitment time, disproportional populations in which TKIs were used, and lack of information on subsequent therapy after first-line EGFR TKI failure [16,17,18,19,20]
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