Lung cancer
ICD-10 C34 · ICD-11 2C25.Z

Treatment of Advanced or Metastatic NSCLC with PD-L1 Expression ≥50% and No Actionable Driver Mutation

This protocol covers patients with advanced or metastatic non-small cell lung cancer (NSCLC) whose tumours express PD-L1 at 50% or more and who test negative for actionable driver mutations with established targeted therapies — a biomarker-defined population where the first-line treatment strategy is distinct.

Clinical scenario Advanced or metastatic NSCLC with PD-L1 expression of 50% or more and no actionable driver mutation present. The high PD-L1 level and absence of a targetable driver mutation together define the appropriate first-line treatment pathway for this patient group.
Treatment approach (partial overview) First-line treatment centres on immunotherapy — specifically PD-1/PD-L1 checkpoint inhibition. Both single-agent and chemotherapy-combination strategies are part of this approach, with the choice informed by histology and patient factors. Preferred agents, combination options, maintenance strategy, and the full sequencing algorithm are available in the complete protocol →
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References

  1. Single-agent pembrolizumab, atezolizumab, or cemiplimab-rwlc are recommended (category 1; preferred) as first-line therapy options for eligible patients with metastatic NSCLC regardless of histology, PD-L1 expression levels of 50% or more, and negative test results for actionable driver mutations that have recommended first-line targeted therapies.
  2. Combination therapy with pembrolizumab plus chemotherapy is recommended (category 1; preferred) as a first-line therapy option in eligible patients with metastatic NSCLC and negative test results for actionable driver mutations, regardless of PD-L1 expression levels.
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