First-line osimertinib compared to earlier generation TKIs in advanced EGFR-mutant NSCLC: A real-world survival analysis

Objectives: This study aimed to compare the overall survival (OS) of patients with advanced EGFR-mutant NSCLC treated with first-line osimertinib versus earlier-generation EGFR tyrosine kinase inhibitors (TKIs) in a real-world setting. Secondary endpoint included OS in patients with uncommon EGFR mutations. Exploratory aim focused on the impact of TKIs sequencing strategies. Methods: We conducted a retrospective cohort study of patients diagnosed with advanced EGFR-mutant NSCLC who started first-line treatment with either osimertinib or another EGFR TKI (afatinib, erlotinib, or gefitinib) at The Christie (Manchester, UK) from January 2014 to May 2023. Data were extracted from electronic health records, and survival outcomes were analysed using Kaplan-Meier estimates and Cox proportional hazards models. Results: We identified 119 patients treated with first-line osimertinib and 217 with other EGFR TKIs. In the whole population, median age was 69 years (IQR 59.8-77) and 67.3 % of the patients had an ECOG 0-1. With a median follow-up of 73.2 months (95 % CI 66.2-115.7) and 30.6 months (95 % CI 26.0-38.4) in the earlier-generation TKIs and the osimertinib groups, respectively, the median OS was comparable (16.6 vs 16.9 months; HR = 1, p = 0.97). Patients with uncommon EGFR mutations (n = 48; 14.3 %) had poorer survival compared to those with common mutations (HR = 1.664, p = 0.002). Amongst patients who received two treatment lines, those who received osimertinib after another TKI had a shorter OS than those who received osimertinib first-line followed by another line of therapy (HR = 2.062, p = 0.022). Conclusion: First-line osimertinib showed comparable OS to earlier-generation EGFR TKIs for advanced EGFRmutant NSCLC. Patients with uncommon EGFR mutations had a poorer survival. Further research is warranted to optimize treatment for patients with uncommon EGFR mutations and to explore the cost-effectiveness of different sequencing approaches.