TARGET-EU: Nivolumab plus ipilimumab with chemotherapy versus pembrolizumab with chemotherapy in patients with non-oncogenic metastatic non-small-cell lung cancer with <1% PD- L1 tumour expression

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  NIVOLUMAB

  IPILIMUMAB

  PEMBROLIZUMAB
• Anatomical Therapeutic Chemical (ATC) code:
  (L01FF01) nivolumab

  nivolumab

  (L01FX04) ipilimumab

  ipilimumab

  (L01FF02) pembrolizumab

  pembrolizumab
• Medical condition to be studied:
  Lung cancer metastatic

Population studied

• Short description of the study population:
  This study is conducted using routinely collected cancer registry data, retrieved from electronic health records (EHR). Data are sourced from the Dutch national cancer registry (IKNL) and include patients who started index or reference treatment between 1-1-2022 and 31-12-2024. The final study population will consist of adults (>18 years) who have a primary diagnosis of non-oncogenic stage IV lung cancer (no prior malignancy), have a recorded PD-L1 tumour expression <1% and a good performance status (ECOG 0-1). The time period for inclusion (treatment started between 1-1-2022 to 31-12-2024) is based on the availability of the index treatment (reimbursed in the Netherlands from 2022) and to ensure a theoretical minimum one year and one month time of data availability for every patient to identify outcomes with the cut-off point at 1-2-2026. Immunotherapy should be started within 90 days from diagnosis. Start of the chemotherapy component is allowed up to 28 before the start of immunotherapy. The index date is the date of first immunotherapy.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Estimated number of subjects:
  1200

Study design details

• Study design:
  This an active comparator cohort study.
• Main study objective:
  The objective of this study is to compare overall survival (OS) of nivolumab plus ipilimumab with chemotherapy versus pembrolizumab with chemotherapy in patients with non-oncogenic metastatic NSCLC and <1% PD-L1 tumour expression.
• Setting:
  This study is conducted using routinely collected cancer registry data, retrieved from electronic health records (EHR) in the period 2022 – 2024. This time frame reflects the period of dual immunotherapy use in routine clinical practice in the Netherlands. The study is set in outpatient hospital care. Data are sourced from all patients diagnosed with cancer in the Netherlands, providing population-based and representative coverage of real-world clinical care.
• Comparators:
  Pembrolizumab plus chemotherapy
• Outcomes:
  Overall survival
• Data analysis plan:
  This study has two Estimands. For Estimand 1, the main estimand supporting decision making, the primary causal effect summary measure is the HR of death from any cause in patients with metastatic non-oncogenic NSCLC with a PD-L1 expression of <1% receiving dual immunotherapy (nivolumab + ipilimumab)+ chemotherapy versus pembrolizumab + chemotherapy as first line of therapy, regardless of treatment discontinuation or treatment switch. The primary analysis will be an inverse probability of treatment weighted (IPTW) Cox proportional hazard model. Sensitivity analyses will be performed to investigate the robustness of the results to assumptions made in the primary analysis. For Estimand 2 the difference in RMST will be estimated using the accelerated failure time (AFT) model with Weibull distribution. Supplementary analyses, including diagnostic and descriptive assessments to support the main analysis, will be displayed to contextualise data and results from the primary and sensitivity analyses. These cover crude and IPTW-adjusted Kaplan Meier curves, weight and propensity score distributions, covariate balance before and after weighting, censoring patterns, proportional hazards diagnostics, Schoenfeld residuals analysis, and positivity checks.
• Summary results:
  Not yet available