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
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 118
- 主要终点
- Progression-free Survival
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-75 years, no restriction on sex.
- •Histologically or cytologically confirmed stage III-IV non-squamous NSCLC, unresectable as assessed by multidisciplinary team (MDT).
- •Presence of EGFR exon 19 deletion (19Del) or L858R mutation, confirmed by ARMS-PCR, NGS, or other validated methods.
- •No prior systemic therapy for lung cancer.
- •ECOG performance status of 0-
- •Estimated life expectancy of at least 6 months.
- •Primary lung tumor size ≥1 cm, with at least one measurable lesion remaining after resection according to RECIST v1.1 criteria.
- •Adequate organ function, including:
- •① Hematologic function: absolute neutrophil count ≥1.5 × 10⁹/L; platelet count ≥100 × 10⁹/L; hemoglobin ≥9.0 g/dL.
- •② Hepatic function: ALT and AST ≤2.5 × ULN (≤5 × ULN if liver metastases are present); total bilirubin ≤1.5 × ULN.
- •③ Renal function: serum creatinine ≤1.5 × ULN, or creatinine clearance ≥50 mL/min (Cockcroft-Gault formula).
- •Adequate pulmonary function (must meet at least one of the following to ensure postoperative reserve):
- •① FEV1 ≥1.2 L (or ≥40% of predicted value);
- •② FEV1/FVC ≥0.7, to exclude severe obstructive ventilatory dysfunction;
- •③ DLCO (diffusing capacity for carbon monoxide) ≥40% of predicted value, to assess diffusion capacity.
- •④ If preoperative FEV1 <1.2 L or DLCO <40%, additional cardiopulmonary exercise testing (e.g., 6-minute walk test, stair climbing test) is recommended to evaluate postoperative pulmonary reserve.
- •Evaluated by the study team and deemed suitable for primary tumor resection.
- •Signed written informed consent and willingness to comply with study protocol.
排除标准
- •Presence of any other known EGFR mutations.
- •Histological evidence of mixed small-cell lung cancer (SCLC) or history of transformation to SCLC.
- •Immunodeficiency: history of primary immunodeficiency disorders, or prior allogeneic organ or bone marrow transplantation.
- •Active brain metastases. Patients with adequately treated brain metastases may be eligible if they are neurologically stable for at least 2 weeks before enrollment, and are either not requiring corticosteroids or receiving a stable or decreasing dose of ≤10 mg prednisone (or equivalent) once daily.
- •Any serious comorbid condition that, in the opinion of the investigator, may interfere with participation in the study or interpretation of study results, including but not limited to: uncontrolled systemic diseases, psychiatric illness, active or uncontrolled infections, or other abnormal findings from laboratory or clinical examinations.
研究组 & 干预措施
Control Group
Participants will receive oral osimertinib at a dose of 80 mg once daily, continued until disease progression or the occurrence of unacceptable toxicity.
干预措施: Osimertinib (Drug)
Intervention Group
Participants will first undergo cytoreductive surgery. After adequate postoperative recovery for 4-6 weeks, they will receive oral osimertinib at a dose of 80 mg once daily, continued until disease progression or the occurrence of unacceptable toxicity.
干预措施: Surgery (Procedure)
Intervention Group
Participants will first undergo cytoreductive surgery. After adequate postoperative recovery for 4-6 weeks, they will receive oral osimertinib at a dose of 80 mg once daily, continued until disease progression or the occurrence of unacceptable toxicity.
干预措施: Osimertinib (Drug)
结局指标
主要结局
Progression-free Survival
时间窗: From randomization until the first documentation of disease progression or death from any cause, whichever occurs first (up to 5 years).
Progression-free survival is defined as the time from randomization to the first documentation of disease progression or death from any cause, whichever occurs first. Disease progression will be assessed by the Independent Radiology Review Committee according to RECIST version 1.1 criteria.
次要结局
- Overall Survival(Randomization to death from any cause (up to 5 years).)
- Objective Response Rate(Randomization until disease progression or death, which ever occurs first (up to 5 years).)
- Disease Control Rate(Randomization until disease progression or death, which ever occurs first (up to 5 years).)
- Adverse Events(From randomization to disease progression or death (up to 5 years).)
- Quality of Life (QoL) evaluated by European Organisation for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30)(Randomization until disease progression or death, which ever occurs first (up to 5 years).)
- Quality of Life (QoL) evaluated by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13)(Randomization until disease progression or death, which ever occurs first (up to 5 years).)
研究者
Jianxing He
Professor
The First Affiliated Hospital of Guangzhou Medical University