Real-world clinical outcomes of first-generation and second-generation epidermal growth factor receptor tyrosine kinase inhibitors in a large cohort of European non-small-cell lung cancer patients

Background First-generation or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are commonly used in EGFR-mutation-positive advanced non-small-cell lung cancer (NSCLC) with no relevant differences in efficacy in randomised clinical trials (RCTs). Patients enrolled to RCTs may differ from NSCLC population in everyday practice. Limited real-world experience (RWE) exists on efficacy of EGFR TKIs in European patient cohorts. Patients and methods In this retrospective study, real-world data of all patients who started first-line EGFR TKIs between 2012 and 2016 in Poland were analysed. The main endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints were an objective response rate and toxicity. Results A total of 620 treatment-naive EGFR mutated patients with stage III/IV NSCLC were analysed with follow-up time of 24.5 months. A significantly longer median PFS (p=0.005) and higher 1-year OS rate (p=0.004) for afatinib (16.4 months and 78.2%) vs gefitinib (10.3 months and 69.1%) and erlotinib (12.1 months and 71.6%) were observed. In multivariate analysis toxicity was predictive for PFS and OS. In patients with adverse events (AEs) versus those without AEs, improved median PFS (13.6 months vs 8.8 months) and median OS (23.6 vs 15.5 months) were observed. Median OS in the group with AE of grades 3-4 and those with AE of grades 1-2 were 42.1 months and 23.4 months, respectively. Conclusion This study represents the largest RWE of first-line TKI therapy in a European country with longer survival of patients receiving second-generation TKI. We confirmed in everyday practice the role of toxicity as a marker of clinical benefit.