WCLC 2025 - Posters & ePosters-EP.12.62 Identification of Optimal Candidates for the FLAURA2 Regimen in EGFR-Mutated NSCLC Based on PFS2 Analysis

Pdf Summary

This study conducted at Kanazawa University Hospital retrospectively analyzed progression-free survival (PFS1 and PFS2) and overall survival (OS) in 87 patients with EGFR mutation–positive non-small cell lung cancer (NSCLC) to identify candidates suitable for the FLAURA2 regimen, which combines osimertinib with chemotherapy. The median PFS1 was 13.9 months, PFS2 was 24.3 months, and OS was 34.3 months. Significantly poorer outcomes were observed in patients presenting with CNS metastases at diagnosis—31% of the cohort—with shorter PFS1, PFS2, and OS compared to those without CNS involvement.<br /><br />Among patients receiving second-line therapy, CNS metastases were associated with shorter PFS2, even in those treated sequentially with EGFR-TKI followed by chemotherapy. Multivariate analysis identified CNS metastases at diagnosis and EGFR mutation subtype (exon 19 deletion vs. L858R) as significant factors influencing PFS2. Patients harboring the L858R mutation had worse outcomes, potentially due to concomitant RBM10 mutations that confer resistance to EGFR-TKIs.<br /><br />The study discusses the limited CNS penetration of chemotherapy agents and acknowledges that while EGFR-TKIs offer CNS efficacy, prognosis remains poor for patients with CNS metastases. The FLAURA2 trial has demonstrated the enhanced effect of combining osimertinib with chemotherapy, especially for CNS lesions, indicating this regimen as promising for such patients.<br /><br />Preclinical data suggest that concurrent osimertinib with cisplatin or pemetrexed exhibits synergistic cytotoxicity and delays resistance onset, contrasting with sequential treatment where EGFR-TKI–induced cell cycle arrest may reduce chemotherapy effectiveness.<br /><br />In conclusion, patients with EGFR L858R mutation and CNS metastases at diagnosis display poor PFS2 on EGFR-TKI monotherapy but respond better to combined chemotherapy and osimertinib as per FLAURA2 trial results. Thus, these findings support using the FLAURA2 regimen in this subset to improve clinical outcomes.

Asset Subtitle

Yuya Murase

Meta Tag

Speaker Yuya Murase

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

EGFR mutation

non-small cell lung cancer

NSCLC

FLAURA2 regimen

osimertinib

chemotherapy

CNS metastases

progression-free survival

L858R mutation

EGFR-TKI resistance