Survival Efficacy of Combined Radiotherapy and Immunotherapy in Patients With Metastatic Non-small Cell Lung Carcinoma

NCT07111104 | Completed

• 1 other identifier: 2024-001-UNEOS-Obs
• Study Type: observational
• Target: 350
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this retrospective, multicenter, observational study is to evaluate the potential clinical benefit of adding radiotherapy (administered either concomitantly or sequentially) to immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC). One promising approach involves the integration of radiotherapy into the treatment plan. Radiotherapy is known not only for its cytotoxic local effects, but also for its ability to modulate the tumor microenvironment, increase antigen presentation, and stimulate systemic immune responses. This study will compare two cohorts of patients with metastatic NSCLC treated in real-world clinical settings. The first cohort includes patients treated with immunotherapy alone, while the second includes those who received immunotherapy in combination with radiotherapy. Radiotherapy may have been administered concurrently or sequentially with respect to immunotherapy, based on clinical judgment. The primary objective is to determine whether the addition of radiotherapy improves progression-free survival (PFS) by at least 30%, compared to immunotherapy alone. This threshold reflects clinically meaningful differences reported in randomized controlled trials in similar populations and treatment lines. Secondary objectives include overall survival (OS) and exploring predictive factors of treatment response, such as patient demographics, tumor characteristics, mutational status, timing of radiotherapy and abscopal effect evaluation, to refine patient selection for future combination strategies. Eligible participants are adults with histologically confirmed metastatic NSCLC, treated with first-line or second-line immunotherapy, and with no prior exposure to immunotherapy. Data will be retrospectively collected from medical records, and treatment arms will be assigned based on actual clinical care paths. Participants will:

• Be retrospectively identified from hospital records.
• Be assigned to one of two cohorts: immunotherapy alone or immunotherapy + radiotherapy (concomitant or sequential).
• Have their data analyzed for OS, PFS, toxicity, and potential predictive biomarkers. The results of this study will contribute to a better understanding of real-world outcomes in metastatic NSCLC patients and may inform future prospective trials evaluating radiotherapy as a modulator of immunotherapy efficacy.

Conditions

Non Small Cell Lung Cancer Metastatic

Keywords

non small cell lung cancer; NSCLC; metastatic; radiotherapy; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS is defined as the time from the first administration of immunotherapy to the date of confirmed disease progression or death from any cause, whichever occurs first. Progression is assessed using imaging (CT scan, PET scan or MRI) according to iRECIST v1.1 criteria.

  Up to 18 months from start of immunotherapy

Secondary Outcomes (6)

• Overall Survivall (OS)

  Up to 18 months from start of immunotherapy

• Objective Response Rate (ORR)

  Up to 18 months from start of immunotherapy

• Objective Response Rate (ORR bis)

  Up to 18 months from start of immunotherapy

• Progression Free Survival 2 (PFS-2)

  Up to 18 months from start of immunotherapy

• Progression Free Survival after Radiotherapy (PFS RT)

  Up to 18 months from end of radiotherapy.

Study Arms (2)

Immunotherapy cohort

This group includes patients with metastatic non small cell lung cancer (NSCLC) who received immune checkpoints inhibitors (Nivolumab, Atezolizumab or Pembrolizumab) without any associated radiotherapy during the course of treatment

Drug: Immunotherapy

Immunotherapy + radiotherapy cohort

This group includes patients with metastatic non-small cell lung cancer (NSCLC) who received immune checkpoint inhibitors (Nivolumab, Atezolizumab, or Pembrolizumab) in combination with radiotherapy. Radiotherapy was delivered either concomitantly or sequentially to immunotherapy.

Drug: Immunotherapy; Radiation: Radiotherapy

Interventions

Immunotherapy DRUG

The immunotherapy intervention consists of treatment with immune checkpoint inhibitors, specifically Nivolumab (OPDIVO), Atezolizumab (TECENTRIQ), Pembrolizumab (KEYTRUDA). These drugs are monoclonal antibodies that block PD-1 or PD-L1 pathways, aiming to enhance the immune system's ability to recognize and destroy cancer cells. The treatment is administered intravenously according to standard dosing schedules.

Also known as: Biological Therapy

Immunotherapy + radiotherapy cohort; Immunotherapy cohort

Radiotherapy RADIATION

The radiotherapy intervention involves targeted delivery of ionizing radiation to metastatic lesions. Radiotherapy may be given either concurrently with immunotherapy or sequentially afterward, depending on the patient's treatment plan. The purpose is to achieve local tumor control and potentially enhance the systemic immune response through immunogenic cell death. Different radiation techniques and dose regimens may be employed based on lesion size, location, and clinical considerations.

Also known as: Radiation Therapy, External Beam Radiotherapy, Radiation Treatment

Immunotherapy + radiotherapy cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with metastatic non-small cell lung cancer receiving immunotherapy at the metastatic stage, with no previous immunotherapy treatment.

You may qualify if:

• Age \>18 years
• Patient with metastatic non-small cell cancer who has received one line of immunotherapy (PEMBROLIZUMAB, ATEZOLIZUMAB and NIVOLUMAB) in stage IV.
• Disease evaluable according to iRECIST v1.1 criteria
• For previously irradiated patients, a non-irradiated lesion evaluable according to iRECIST
• WHO (World Health Organization) score less than or equal to 2.

You may not qualify if:

• Composite cancer, small cell lung cancer
• Not metastatic at the time of immunotherapy
• Has already received one line of immunotherapy for non-small cell lung cancer: antibody against Programmed cell Death protein 1 (anti-PD-1), antibody against Programmed Death-Ligand 1 or 2 (anti-PD-L1 and anti-PD-L2), antiboby against Cluster of Differentiation 137 (anti-CD137), antibody against Cytotoxic T-lymphocyte-antigen-4 (anti-CTLA-4)) .
• Second active cancer under treatment
• Immunotherapy for another cancer
• Withdrawal of consent
• \- Patients treated with DURVALUMAB, on the basis of its marketing authorisation in non-small cell lung cancer and in the adjuvant treatment of NSCLC treated with concomitant radiochemotherapy.

Sponsors & Collaborators

• Hopitaux Prives de Metz, Groupe UNEOS: lead

Study Sites (1)

Hopitaux Privés de Metz - UNEOS

Vantoux, 57040, France

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

Immunotherapy; Biological Therapy; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunomodulation; Therapeutics

Study Officials

• Ariane Guignard, Resident

  Hopitaux privés de Metz - UNEOS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2025
• First Posted: August 8, 2025
• Study Start: October 14, 2024
• Primary Completion: October 14, 2024
• Study Completion: April 28, 2025
• Last Updated: August 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)