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FIN-EGFRprint: a Finnish real-world study on treatments and outcomes in advanced NSCLC with common EGFR mutations
Aija Knuuttila1, Lalli O Nurmi2, Petri M Vänni2
1Department of Pulmonary Medicine, Heart and Lung Center, and Cancer Center, Helsinki University Central Hospital, Helsinki, Finland.
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-world survival with TKIs remains lower than clinical trials results emphasizing the unmet need.
Insights
The use of advanced EGFR tyrosine kinase inhibitors (TKIs) has significantly improved real-world outcomes for advanced non-small cell lung cancer (aNSCLC) patients with common EGFR mutations. Survival times have increased, highlighting the benefit of newer generation TKIs.
Area of Science:
- Oncology
- Pharmacology
Background:
- Advanced non-small cell lung cancer (aNSCLC) treatment has evolved with the advent of epidermal growth factor receptor (EGFR) mutations and tyrosine kinase inhibitors (TKIs).
- First-, second-, and third-generation EGFR TKIs have become standard first-line therapies for patients with common EGFR mutations.
Purpose of the Study:
- To evaluate real-world outcomes in aNSCLC patients with common EGFR mutations.
- To assess improvements in time to next treatment (TTNT) and overall survival (OS) over time with the introduction of different generations of EGFR TKIs.
Main Methods:
- Retrospective observational study of 379 aNSCLC patients with EGFR exon 19 deletion or L858R mutations.
- Analysis of TTNT and OS from first-line treatment initiation using Kaplan-Meier and Cox regression.
- Stratification into three cohorts based on diagnosis date and TKI availability (1st-gen: 2010-2016, 2nd-gen: 2017-2020, 3rd-gen: 2020-2023).
Main Results:
- First-line chemotherapy use decreased from 32% to 6%, while 3rd-gen TKI use rose to 80% in the latest cohort.
- Median TTNT improved significantly from 9.7 to 21.6 months (HR: 0.46, p < 0.001).
- Median OS increased from 19.1 to 29.3 months (HR: 0.56, p = 0.002).
Conclusions:
- Real-world outcomes for aNSCLC with common EGFR mutations have improved, attributed to the shift towards third-generation TKIs.
- Despite improvements, real-world survival remains below clinical trial results, indicating an unmet need.
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