Atezolizumab in Large Cell Neuroendocrine Carcinoma
Condition: Large Cell Neuroendocrine Carcinoma of the Lung
MeSH terms: Carcinoma; Carcinoma, Neuroendocrine; Lung Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      Large Cell Neuroendocrine Carcinoma (LCNEC) is a rare and aggressive form of cancer that
      presents significant challenges regarding treatment options and prognosis. In this trial, the
      effectiveness of Atezolizumab in treating metastatic LCNEC was evaluated. Atezolizumab is an
      anti-PD-L1 antibody that has shown promising results in other types of cancer, such as
      small-cell lung Cancer and non-small-cell lung cancer. The trial aimed to assess the efficacy
      and safety of atezolizumab in combination with chemotherapy as a potential treatment option
      for treatment-naive patients with metastatic LCNEC The trial was conducted as an open-label,
      non-randomized study, comparing Atezolizumab plus platinum etoposide to platinum etoposide
      alone in patients with metastatic LCNEC.
    

Detailed description: 
      This trial is a prospective clinical study to evaluate the effectiveness of a combination
      treatment regimen for patients with metastatic Large Cell Neuroendocrine Carcinoma (LCNEC)
      originating from the lung. The trial occurred between March 2018 and August 2022 at the 3rd
      Department of Medicine, Kapodistrian Medical School of Athens. The institutional review board
      of Sotiria Chest Diseases Hospital of Athens approved it. The trial adhered to Good Clinical
      Practice guidelines and the Declaration of Helsinki, and all patients or their legal
      representatives provided informed consent.

      Patients:

      The trial enrolled patients with metastatic LCNEC originating from the lung. Eligible
      patients had not received prior systemic treatment for LCNEC. Patients with brain metastases
      at diagnosis underwent Whole Brain Radiotherapy (WBRT) before starting systemic treatment.

      Study Design:

      The experimental group received a combination treatment regimen consisting of four cycles of
      Carboplatin, Etoposide, and Atezolizumab every 21 days.

      Patients who achieved stable disease (SD) or a response (partial or complete) continued
      maintenance treatment with Atezolizumab until disease progression or discontinuation due to
      severe adverse events.

      The control group received four cycles of Carboplatin and Etoposide. Immune checkpoint
      inhibitors were not allowed in later lines of treatment for the control group.

      Response to therapy was assessed using CT scans and physical evaluations.

      Endpoints:

      Progression Free Survival (PFS): The time from treatment initiation to disease progression or
      death.

      Overall Survival (OS): The time from treatment initiation to death. Overall Response Rate
      (ORR): The percentage of patients with a complete or partial response based on RECIST v1.1
      criteria.

      Duration of Response (DoR): The length of time the disease responded to treatment without
      progression on imaging studies.

      Procedure:

      Patients were treated at the 3rd Department of Medicine, Kapodistrian Medical School of
      Athens.

      Approval for immunotherapy was obtained from the National Organisation for the Provision of
      Health Services (EOPYY) for each patient.

      Blood samples for miR-375 and miR-21 analysis were collected at specific time points and
      processed according to standard procedures.

      Analysis of miRNA expression was performed using the miRCURY LNA SYBR Green PCR Kit.

      Statistical Analysis:

      Rstudio was used for statistical analysis. The trial did not include a power analysis. The
      intention-to-treat principle was followed. Kaplan-Meier methods and Cox Regression survival
      analysis were used to estimate PFS and OS.

      An analysis of the significance of the difference in characteristics between the experimental
      and control groups was conducted.

      miR-21 and miR-375 Analysis:

      Control samples for miR-21 and miR-375 were collected from volunteers without a cancer
      diagnosis, matching age with LCNEC patients.

      Blood samples were collected at specific time points and processed to isolate plasma.

      RNA was isolated from plasma samples, followed by cDNA synthesis and miRNA quantification
      using the miRCURY LNA SYBR Green PCR Kit.

      MiR-103a-3p was used as a reference gene. Real-time PCR was performed to quantify miRNAs, and
      the results were expressed relative to the control group.
    

Intervention name(s): Atezolizumab; Carboplatin; Etoposide
Intervention type(s): Drug; Drug; Drug
Intervention description(s): TECENTRIQ C/S.SOL.IN 1200MG/VIAL (20ML) 1 VIAL x 20ML; SOL.INF 450MG/45ML VIAL ΒΤx1VIALx45ML; ETOPOSIDE/PHARMACHEMIE SOL.INF 100MG/5ML VIAL BT x 10 VIALS x 5 ML
Other intervention name(s): Tecentriq; CARBOPLATIN/HOSPIRA
Intervention MeSH terms: Carboplatin; Etoposide; Atezolizumab
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Atezolizumab; Immunotherapy; LCNEC; Large Cell Neuroendocrine Carcinoma; Immune Checkpoint Inhibitors; miR375