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

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

Patients with advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 at 50% or more — and who test negative for actionable driver mutations — represent a clinically distinct group with specific evidence-based first-line recommendations.

Clinical Scenario

This protocol applies to patients with advanced or metastatic NSCLC confirmed to have PD-L1 expression of 50% or more and no actionable driver mutation for which a targeted therapy is indicated. Biomarker testing to establish PD-L1 status and driver mutation results is central to correctly identifying this population.

Preferred first-line options for eligible patients in this setting are defined by category-1 evidence and are independent of histologic subtype.

Treatment Approach

For patients who experience disease progression after first-line therapy, the protocol addresses selected chemotherapy options for subsequent treatment. Guidance is also provided on whether re-challenge with checkpoint inhibitor therapy is appropriate following progression on a PD-1/PD-L1 inhibitor.

Full regimen selection, sequencing criteria, and eligibility details are available in the complete protocol.
Instant Access to Structured Evidence-Based Regimens
References

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.

If patients have disease progression on PD-1/PD-L1 inhibitor therapy (± chemotherapy), then using a PD-1/PD-L1 inhibitor is not recommended for subsequent therapy.

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