Patients with advanced or metastatic non-small cell lung cancer (NSCLC) whose tumours test negative for actionable driver mutations and show PD-L1 expression below 1% represent a distinct clinical sub-population. Evidence from randomised trials has defined a specific preferred first-line strategy for this group.
Clinical scenario: Advanced or metastatic NSCLC confirmed negative for actionable driver mutations, with PD-L1 tumour proportion score less than 1%. This population is addressed by evidence-based first-line recommendations regardless of histological subtype.
Current evidence supports combining platinum-based chemotherapy with an immune checkpoint inhibitor as the preferred first-line approach in this setting. For patients with contraindications to immunotherapy, an alternative chemotherapy-based strategy applies. Full regimen selection, histology-dependent options, sequencing, and maintenance are detailed in the structured protocol.
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.
A pooled analysis of three randomized trials (ie, KEYNOTE-189, KEYNOTE-407, KEYNOTE-021) in patients with metastatic NSCLC and PD-L1 levels less than 1% showed that overall survival was improved in those receiving pembrolizumab plus chemotherapy versus chemotherapy alone.
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