NCT07177092

Primary Tumor Resection Plus Osimertinib in Advanced EGFR-mutant Non-small Cell Lung Cancer

Efficacy and Safety of Primary Tumor Resection Combined With Osimertinib in Patients With Advanced EGFR-mutant Non-small Cell Lung Cancer: A Randomized Controlled Study

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 118 (estimated)
• Sponsor: Jianxing He · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This study is designed to explore whether resecting the primary lung cancer, followed by osimertinib, can improve outcomes for patients with advanced non-small cell lung cancer (NSCLC) harboring sensitizing EGFR mutations (exon 19 deletion or L858R). Patients with stage III-IV NSCLC will be included and randomly assigned to receive either surgery to remove the primary lung cancer followed by osimertinib, or osimertinib alone. All patients will continue treatment until disease progression or they need to stop for another reason. The primary outcome being studied is progression-free survival (PFS). Secondary outcomes include overall survival (OS), objective response rate (ORR), disease control rate (DCR), adverse effects (AEs), serious adverse effects (SAEs) and quality of life (QoL). The findings from this study may help determine whether surgery combined with EGFR tyrosine kinase inhibitor (TKI) provides more benefit than EGFR-TKI alone for patients with EGFR-mutant advanced NSCLC.

Detailed description

Osimertinib is a third-generation EGFR-TKI that has become one of the standard first-line treatments for patients with advanced NSCLC harboring sensitizing EGFR mutations such as exon 19 deletion and L858R substitution. Although osimertinib significantly improves survival outcomes, most patients eventually experience disease progression because of drug resistance, and long-term survival remains limited. Surgical resection has traditionally been reserved for early-stage NSCLC. However, emerging evidence suggests that removing the primary tumor, even in the setting of advanced disease, may help reduce tumor burden, delay resistance, and potentially enhance the effectiveness of systemic therapies. To date, there is little high-quality evidence from randomized trials evaluating the role of primary tumor resection in combination with EGFR-TKI for patients with unresectable stage III-IV NSCLC harboring sensitizing EGFR mutations. This randomized, open-label, phase 2 study is designed to evaluate whether combining primary tumor resection with osimertinib provides superior clinical outcomes compared with osimertinib alone in patients with advanced EGFR-mutant NSCLC. Approximately 118 eligible patients will be randomized in a 1:1 ratio to receive either surgery followed by osimertinib or osimertinib monotherapy. Treatment will continue until disease progression or discontinuation criteria are met. The primary outcome is PFS assessed by independent radiology review according to RECIST v1.1. Secondary outcomes include OS, ORR, DCR, AEs, SAEs and QoL. Statistical analysis will include Kaplan-Meier estimation of median PFS with 95% confidence intervals, log-rank testing for comparing differences between the two treatment groups, and Cox proportional hazards models for calculating hazard ratios. Stratification will be performed based on clinical stage, EGFR mutation type, tumor size, and baseline demographic characteristics. The results of this trial are expected to provide high-level evidence on whether surgery combined with EGFR-TKI offers additional clinical benefit over standard EGFR-TKI alone in advanced EGFR-mutant NSCLC.

Conditions

• Non-Small Cell Lung Cancer
• EGFR

Interventions

Type	Name	Description
PROCEDURE	Surgery	① Preoperative evaluation must confirm resectability. Thoracoscopic minimally invasive surgery will be performed, with the surgical approach selected according to disease conditions, such as lobectomy, segmentectomy, wedge resection, or sleeve resection; ② Systematic mediastinal lymph node dissection or lymph node sampling (based on preoperative imaging and intraoperative evaluation) must be performed; ③ Postoperative recovery must be adequate (postoperative complications ≤ Clavien-Dindo grade II).
DRUG	Osimertinib	Dose: 80 mg orally, once daily, until disease progression or the occurrence of unacceptable toxicity. The dose should be administered at approximately the same time each day, at 24-hour intervals.

Timeline

• Start date: 2025-09-08
• Primary completion: 2028-10-01
• Completion: 2030-12-01
• First posted: 2025-09-16
• Last updated: 2025-09-16