Aija Knuuttila, Monica H Ekblom, Lalli O Nurmi, Anna Bonin, Eija K Heikkilä, Maria Silvoniemi
EGFR subtype did not affect outcomes in early-stage NSCLC, while Del19 mutations and first-line third-generation TKIs were associated with better outcomes in advanced disease. Younger patients had higher rates of CNS and bone metastases, which were associated with shorter OS.
BACKGROUND AND PURPOSE: The aim of the study was to compare overall survival (OS) and time to next treatment (TTNT) of epidermal growth factor receptor (EGFR) mutation positive Non-Small Cell Lung Cancer (NSCLC) patients from start of first therapy, by EGFR mutational sub-type, disease stage at first diagnosis (early vs. advanced stage), first treatment and metastatic sites. Patient/material and methods: This retrospective observational study utilized patient-level data from hospital data lakes at two university hospital districts in Southern Finland on EGFR-mutation-positive NSCLC patients diagnosed between 2017 and 2023. OS and TTNT were analysed from start of first therapy using Kaplan-Meier, multivariable Cox proportional hazard models and log-rank test.
RESULTS: Among 544 EGFR-mutant NSCLC patients, 42% had early-stage disease. In early-stage NSCLC, OS did not differ significantly between Del19 and L858R mutations, and surgery was the only initial treatment associated with improved OS, with Del19 providing no additional survival benefit. In advanced-stage NSCLC, L858R mutation was a risk factor for shorter OS compared to Del19 (hazard ratio [HR]: 2.01 95% confidence interval [CI]: 1.34-3.02, p = 0.001). First-line third-generation tyrosine kinase inhibitor (TKI) showed improved OS compared to first-generation TKI (HR: 0.46 95% CI: 0.28-0.78, p = 0.004). Younger patients more often had central nervous system (CNS) and bone metastases. CNS and liver metastases at diagnosis were linked to shorter OS (5.0 and 8.1 months, respectively).
INTERPRETATION: EGFR subtype did not affect outcomes in early-stage NSCLC, while Del19 mutations and first-line third-generation TKIs were associated with better outcomes in advanced disease. Younger patients had higher rates of CNS and bone metastases, which were associated with shorter OS.