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Patients with stage IV squamous non-small cell lung cancer (NSCLC) were historically treated with first-line platinumbased therapy. Median overall survival (OS) with these regimens was 10–12 months and 5-year OS was estimated at 2% (1,2). Standard of care for patients with squamous NSCLC who developed progressive disease on platinumbased doublets was either (I) docetaxel with or without ramucirumab or (II) gemcitabine (3,4). Subsequently, four randomized phase III trials demonstrated significant improvements in survival when compared to docetaxel for patients receiving monotherapy with a programmed death-1 (PD-1) axis inhibitor (5-8). As a result, PD-1 axis inhibitors became the preferred second-line therapy after development of progressive disease on a platinum-based doublet. Immune checkpoint inhibitors were then evaluated as initial treatment in combination with platinum-based chemotherapy. The PD-1 inhibitor pembrolizumab added to first-line platinum-based chemotherapy demonstrated superior objective response rate (ORR), progressionfree survival (PFS) and OS in non-squamous NSCLC (9). Similarly, three phase III trials evaluated the addition of an immune checkpoint inhibitor to platinum-based doublets in advanced squamous NSCLC (10-13). The cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor ipilimumab combined with carboplatin and paclitaxel did not result in improved PFS or OS when compared to chemotherapy alone (10). IMpower131 evaluated the addition of the programmed death ligand-1 (PD-L1) inhibitor atezolizumab to carboplatin plus nab-paclitaxel. IMpower131 demonstrated a PFS benefit for the addition of atezolizumab, but no OS benefit (11,12). KEYNOTE-407, which is the focus of this editorial commentary, evaluated the addition of pembrolizumab to carboplatin plus taxane. KEYNOTE-407 demonstrated an improvement in both PFS and OS for the addition of pembrolizumab to chemotherapy (13).

KEYNOTE-407: changing the way we treat stage IV squamous non-small cell lung cancer