Treatment of Advanced or Metastatic NSCLC with PD-L1 Expression 1–49% and No Actionable Driver Mutation

This protocol addresses a specific sub-population of patients with non-small cell lung cancer at an advanced or metastatic stage, defined by a distinct PD-L1 expression range and the absence of actionable driver mutations — a profile that shapes both first-line therapy selection and subsequent management.

Clinical scenario

Advanced or metastatic non-small cell lung cancer with PD-L1 expression of 1% to 49% and no actionable driver mutation. Molecular profiling to confirm the absence of driver mutations and quantify PD-L1 expression is essential before therapy selection. In this group, first-line combination strategies carrying a high level of evidence and preferred status are available for eligible patients.

Treatment approach (partial)

When disease progresses in this setting, subsequent therapy options include select chemotherapy agents, with considerations that differ by histologic subtype. There are also specific restrictions on the re-use of checkpoint inhibitor therapy based on prior immunotherapy exposure.

Full sequencing, eligibility criteria, and complete regimen details are in the structured protocol ↓

Instant Access to Structured Evidence-Based Regimens

References

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.

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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