Overall survival after treatment with first-line osimertinib for EGFR-mutant advanced NSCLC in the US

Osimertinib is approved for first-line treatment of EGFR-mutated advanced non-small cell lung cancer (NSCLC). In the FLAURA study, median overall survival (OS) was 38.6 months and 2-year landmark OS was 74%. We assessed OS following first-line osimertinib using real-world data from large longitudinal US oncology databases.

This retrospective cohort study used electronic medical records from ConcertAI, Flatiron, and COTA. Patients with newly-diagnosed advanced/metastatic disease with exon 19 deletions or exon 21 L858R substitutions who initiated first-line osimertinib monotherapy between 18-Apr-2018 and 31-Oct-2022 were eligible. Patients were followed up until death, loss to follow-up, or 31-Oct-2023. Mortality data were captured from multiple sources from each database, ensuring completeness. OS was estimated using the Kaplan-Meier method.

432 patients from ConcertAI, 636 from Flatiron, and 234 from COTA were included (Table). Median age ranged from 68-71 years, 67%-70% were female, ECOG score of 0-1 in 49%-70%, and 34%-39% had CNS metastases. The 24-month survival rate (95% CI) was 57% (53-63) in ConcertAI, 57% (53-61) in Flatiron, and 60% (53-67) in COTA (Figure) with corresponding median OS of 27.7, 28.8, and 29.2 months, respectively. Among patients with ECOG 0 or 1, the median OS was 30.7, 30 and 29.1 months, respectively. Between 26%-32% of patients died prior to 2nd line-of-therapy. Older age, CNS metastases, liver metastases, TP53 comutations, exon 21 L858R, and ECOG ≥2 were associated with higher mortality and shorter median OS. A pooled analysis including additional subgroups is underway.

We observed that real-world OS for osimertinib is lower than observed in clinical trial settings. Between one quarter and one third of patients die prior to receiving 2nd line-of-therapy. These results highlight the pressing need for innovative treatments to improve survival.