A Study of Osimertinib-based Adaptive Treatment Guided by ctDNA EGFRm+ Monitoring in NSCLC

Locally advanced or metastatic EGFR mutation-positive (EGFRm) non-small cell lung cancer (NSCLC) (Stage IIIB, IIIC, IV, or recurrent) has a poor prognosis. The 5-year survival rate for metastatic disease is only 8.9%. While combination therapy with osimertinib and platinum-pemetrexed chemotherapy, as validated by the FLAURA2 trial, has demonstrated improved progression-free survival (PFS), it also introduces increased toxicity, treatment burden, and reduced quality of life. Notably, a subset of patients-approximately 25-30%-achieves long-term benefit from osimertinib monotherapy alone, highlighting the potential to personalize treatment intensity. Emerging evidence supports circulating tumor DNA (ctDNA) as a dynamic biomarker for guiding therapy. Analyses from FLAURA2 and other studies have shown that early ctDNA EGFRm clearance strongly correlates with superior PFS and can identify patients who may not require continuous combination therapy. Adaptive strategies based on ctDNA clearance have enabled treatment de-escalation in early-stage and advanced NSCLC settings, maintaining efficacy while reducing toxicity. This trial builds on that rationale, aiming to validate ctDNA-guided adaptive therapy to balance efficacy, safety, and quality of life in EGFRm NSCLC.