Background and purpose

The treatment of advanced non-small cell lung cancer (aNSCLC) with common epidermal growth factor receptor (cEGFR) mutations has evolved substantially over the last 15 years, with the discovery of activating epidermal growth factor receptor (EGFR) mutations and introduction of first-, second- and third generation (gen) EGFR tyrosine kinase inhibitors (TKIs) as first-line therapy. This retrospective observational study aimed to evaluate whether the introduction of these treatments has led to improved ‘real-world’ outcomes over time by analysing time to next treatment (TTNT) and overall survival (OS).

Patient/material and methods 

Patients (n = 379) with EGFR exon 19 deletion (Del19) or exon 21 L858R (L858R) substitution and aNSCLC were identified from two Finnish university hospital data lakes between 2010 and 2023. TTNT and OS were analysed from first-line treatment initiation using Kaplan–Meier survival and multivariable Cox regression analyses. Patients were stratified into three cohorts based on date of diagnosis and which TKIs were available at that time (1st-gen: 2010–2016, 2nd-gen: 2017–2020 and 3rd-gen: 2020–2023).

Results

The use of chemotherapy as first-line therapy declined from 32% (2010–2016) to 6% (2020–2023), while 80% of patients received 3rd-gen TKIs as first-line treatment in 2020–2023. Median TTNT improved over time (9.7 to 13.2 to 21.6), with a significant improvement in 2020–2023 versus 2010–2016 (HR: 0.46; 95% CI: 0.33–0.64; p < 0.001). Median OS also increased over time (19.1 to 23.9 to 29.3 months) and was significantly higher in 2020–2023 versus 2010–2016 (HR: 0.56; 95% CI: 0.39–0.82; p = 0.002).

Interpretation

​​​​​​​‘Real-world’ treatment outcomes for aNSCLC with cEGFR mutations have improved over time likely due to the transition from 1st- to 3rd-gen TKIs. However, real-word survival with TKIs remains lower than clinical trials results emphasizing the unmet need.