Abstract
BACKGROUND: Combination therapy with osimertinib and platinum-based chemotherapy has become the standard first-line treatment for patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC), as demonstrated in the FLAURA2 trial. However, optimal strategies to enhance long-term disease control, particularly the role of local consolidative therapy (LCT), remain unclear. This study aims to evaluate the clinical outcomes and safety of LCT for the primary tumor in patients with EGFR-mutant advanced NSCLC following disease control with first-line osimertinib plus chemotherapy. METHODS: This is a prospective, single-arm, open-label phase II study evaluating the clinical impact of LCT for primary tumors in patients with EGFR-mutant advanced NSCLC who achieve disease control after four cycles of osimertinib plus chemotherapy. LCT (surgery or radiotherapy) will be performed based on multidisciplinary evaluations. Circulating tumor DNA (ctDNA) will be assessed before and after induction therapy. The primary endpoint is progression-free survival (PFS). The secondary endpoints include overall survival (OS), local control rate, toxicity, and patterns of failure. Exploratory analyses will evaluate the association between ctDNA status and clinical outcomes. DISCUSSION: This study aims to elucidate the role of primary tumor-directed local therapy in a real-world population, including patients beyond those with oligometastatic disease. By integrating clinical outcomes with key patient characteristics, it further seeks to define the clinical utility of LCT and identify the patient populations most likely to benefit from its incorporation following systemic disease control with EGFR-tyrosine kinase inhibitor (TKI)-based combination therapy. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT07073365).