Background and Importance A total of 10–40% of non-small-cell lung cancer (NSCLC) tumours harbour EGFR-sensitising mutations. EGFR tyrosine-kinase inhibitors (TKIs) inhibit the proliferation of tumour cells via binding to EGFR specifically and show favourable therapeutic effects on advanced EGFR-mutated NSCLC. The presence of the T790M variant reduces the ability of the reversible EGFR-TKIs. Osimertinib is an orally taken third-generation EGFR-TKI which can form an irreversible covalent bond via the cysteine 797 residue and T790M or other EGFR mutations. Osimertinib has showed an impressive antitumour activity in treatment-naïve advanced NSCLC harbouring EGFR-TKI-sensitising mutations.

Aim and Objectives The aim of the study was to evaluate the effectiveness and safety of osimertinib in patients with EGFR mutation positive NSCLC.

Observational retrospective study All patients with NSCLC undergoing treatment with osimertinib were included (July 2017 to August 2022). Demographic variables: age and sex. Clinical variables: diagnosis, stage, performance status (PS) according ECOG scale, line of treatment, and dose; and other variables: smoking. Overall survival (OS) and progression-free survival (PFS) were analysed using Kaplan-Meier. Adverse events (AE) were also assessed.

Results 39 patients were included with activating EGFR mutations (25.6% T790M), average age was 64.6±11.1 years, 76.9% were women. NSCLC stage was IV in 100% of patients, 23.1% suffered from brain metastases, and 79.5% had ECOG-PS 0–1. Patients started treatment with osimertinib as first-line therapy in 66.6%, 23.1% as second-line and 10.2% as third-line. Previous therapies received: erlotinib (n=3), gefitinib (n=5), afatinib (n=5), chemotherapy (n=4). 17.9% underwent osimertinib dose-reduction mainly due to pneumonitis. 38.5% were past smokers and 17.9% smokers.Median PFS was 10 months (95% CI 4.0–16.0) and OS 28 months (95% CI 14.1–41.8).84.6% of patient had at least one AE of any grade. Most frequent AE were G1–2 asthenia (46.1%), G1–2 cutaneous (35.9%), and G1–2 diarrhoea (30.8%).

Conclusion and Relevance Osimertinib demonstrates a PFS similar to that observed in the second-line AURA-3 trial, although it is lower than the survival outcomes reported in the first-line FLAURA trial. These findings are reasonable when considering our comprehensive dataset, which encompasses both pre-treated and brain metastatic populations. Additionally, osimertinib exhibits a favourable toxicity profile. Given the limited sample size, further investigations are needed to validate these findings.

Conflict of Interest No conflict of interest.