Yifeixiaoji decoction as an adjunct to osimertinib therapy in advanced EGFR-mutated NSCLC: protocol for a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Although EGFR-TKIs have substantially improved outcomes in EGFR-mutated advanced NSCLC, acquired resistance ultimately leads to treatment failure in most patients. Yifeixiaoji Decoction (YFXJD), a traditional Chinese herbal formulation, has shown promise as an adjunctive strategy; however, evidence from prospective clinical studies for this specific formula remains limited. We therefore designed this trial to assess whether YFXJD could prolong progression-free survival when added to standard osimertinib therapy in advanced NSCLC.

METHODS: A total of 200 patients with stage IV EGFR-mutant NSCLC will be enrolled in a randomized, double-blind, placebo-controlled trial and allocated 1:1 to receive standard osimertinib therapy combined with either YFXJD granules or matched placebo. The primary endpoints is progression-free survival. Key secondary endpoints include change in TCM syndrome score, objective response rate, quality of life (EORTC QLQ-C30/LC13), safety (NCI CTCAE v5.0), and exploratory peripheral blood biomarker analyses.

EXPECTED RESULTS: This trial will provide prospective evidence regarding the efficacy and safety of YFXJD as an adjunct to osimertinib therapy in patients with advanced EGFR-mutant NSCLC and will determine whether this approach influences clinical outcomes.

CLINICAL TRIAL REGISTRATION: https://itmctr.ccebtcm.org.cn, ITMCTR2025002306.