Effectiveness of Atezolizumab in Large Cell Neuroendocrine Carcinoma of the Lung and the Value of miR21 and miR-375 as Biomarkers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 22
- 试验地点
- 4
- 主要终点
- Progression-free survival
研究概览
简要总结
Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a rare and aggressive malignancy with limited prospective evidence to guide systemic treatment. This prospective, non-randomized, real-world study evaluated the effectiveness and safety of atezolizumab in combination with platinum-etoposide chemotherapy in treatment-naïve patients with metastatic lung-derived LCNEC.
Patients who received atezolizumab were treated with carboplatin, etoposide, and atezolizumab, followed by atezolizumab maintenance in patients without disease progression for up to 24 months, or until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision, whichever occurred first. Patients in the control cohort received carboplatin and etoposide alone.
The main clinical outcomes were progression-free survival, overall survival, overall response rate, and duration of response. Exploratory translational analyses included plasma microRNA assessment, including miR-375 and miR-21, in available blood samples.
详细描述
This is a prospective, non-randomized, real-world clinical study evaluating the effectiveness and safety of atezolizumab in combination with platinum-etoposide chemotherapy in patients with treatment-naïve metastatic large-cell neuroendocrine carcinoma (LCNEC) originating from the lung.
The study was conducted at the 3rd Department of Medicine, National and Kapodistrian University of Athens, Sotiria General Hospital for Chest Diseases, Athens, Greece. Consecutive eligible patients were enrolled between November 2019 and August 2022. Final clinical follow-up for the updated long-term survival analysis was performed with a data cut-off date of September 1, 2025.
The protocol was approved by the Institutional Scientific Council and Ethics Committee of Sotiria General Hospital and was conducted in accordance with Good Clinical Practice principles and the Declaration of Helsinki. All patients provided written informed consent before enrollment.
Eligible patients were adults with histologically confirmed metastatic lung-derived LCNEC, no prior systemic treatment for metastatic disease, ECOG performance status 0-2, and measurable disease according to RECIST v1.1. Patients with brain metastases at diagnosis were eligible after appropriate management, including whole-brain radiotherapy when clinically indicated.
Because atezolizumab was not approved for metastatic LCNEC, access to atezolizumab was obtained through individual off-label reimbursement requests submitted to the Greek National Organization for Healthcare Services Provision (EOPYY). Patients granted reimbursement approval received carboplatin, etoposide, and atezolizumab, whereas patients not granted approval received carboplatin and etoposide alone and served as a contemporaneous real-world control cohort. No study drug was provided through a sponsor-funded or industry-sponsored access programme.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Cohorts A and B:
- •Inclusion Criteria:
- •Histologically confirmed Stage IV (metastatic) or unresectable locally advanced LCNEC
- •No prior treatment
- •With or without brain metastasis, if symptomatic patients should be treated with WBRT first
- •Performance Status ≤ 2
- •Life expectancy > 3 months
- •Written informed consent
- •Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
排除标准
- •Prior treatment with chemotherapy, immunotherapy, targeted small molecule therapy, or radiation therapy (except WBRT for brain metastasis from LCNEC)
- •Active or history of autoimmune disease or immune deficiency
- •Treatment with systemic immunosuppressive medications with the following exceptions:
- •Patients who have received acute, low-dose systemic immunosuppressant medication (≤ 10 mg/day oral prednisone or equivalent) or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Medical Monitor approval has been obtained.
- •Major surgical procedure other than for diagnosis within 4 weeks before initiation of study treatment, or anticipation of need for a major surgical procedure during the study
- •Active malignancy or malignancy within 3 years
- •Active tuberculosis
- •Current severe, uncontrolled systemic disease other than cancer
- •Known clinically significant liver disease
- •Treatment with any other investigational agent or participation in another clinical study with therapeutic intent
研究组 & 干预措施
Arm A
Carboplatin AUC 5 on day 1 plus etoposide 100 mg/m² on days 1-3 every 21 days for 4-6 cycles, with atezolizumab 1200 mg every 21 days. Patients without disease progression after induction therapy continued atezolizumab maintenance for a maximum duration of 24 months, or until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision, whichever occurred first.
干预措施: Atezolizumab (Drug)
Arm A
Carboplatin AUC 5 on day 1 plus etoposide 100 mg/m² on days 1-3 every 21 days for 4-6 cycles, with atezolizumab 1200 mg every 21 days. Patients without disease progression after induction therapy continued atezolizumab maintenance for a maximum duration of 24 months, or until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision, whichever occurred first.
干预措施: Carboplatin (Drug)
Arm A
Carboplatin AUC 5 on day 1 plus etoposide 100 mg/m² on days 1-3 every 21 days for 4-6 cycles, with atezolizumab 1200 mg every 21 days. Patients without disease progression after induction therapy continued atezolizumab maintenance for a maximum duration of 24 months, or until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision, whichever occurred first.
干预措施: Etoposide (Drug)
Arm B
Carboplatin AUC 5 on day 1 plus etoposide 100 mg/m² on days 1-3 every 21 days for 4-6 cycles, followed by observation. Subsequent treatment at disease progression was administered according to standard-of-care practice and physician judgment.
干预措施: Carboplatin (Drug)
Arm B
Carboplatin AUC 5 on day 1 plus etoposide 100 mg/m² on days 1-3 every 21 days for 4-6 cycles, followed by observation. Subsequent treatment at disease progression was administered according to standard-of-care practice and physician judgment.
干预措施: Etoposide (Drug)
结局指标
主要结局
Progression-free survival
时间窗: Through study completion, an average of 3 years
Progression Free Survival (PFS) was defined as the time from treatment initiation to disease progression οr death. Patients alive without progression at the last follow-up were censored at the date of the deadline for follow-up
Overall survival
时间窗: Through study completion, an average of 3 years
Overall survival (OS) was defined as the time from treatment initiation to death, and patients alive during the last follow-up were censored at the date of the deadline for follow-up
Progression-free survival
时间窗: From treatment initiation through study completion/data cut-off, assessed up to 70 months.
Progression-free survival was defined as the time from treatment initiation to radiographic disease progression according to RECIST v1.1 or death from any cause, whichever occurred first. Patients without documented disease progression or death were censored at the date of last disease assessment or last follow-up.
Overall survival
时间窗: From treatment initiation through study completion/data cut-off, assessed up to 70 months.
Overall survival was defined as the time from treatment initiation to death from any cause. Patients alive at the time of data cut-off were censored at the date of last confirmed survival follow-up.
次要结局
- Overall Response Rate(From treatment initiation through study completion/data cut-off, assessed up to 70 months.)
- Duration of Response(From treatment initiation through study completion/data cut-off, assessed up to 70 months.)