Improving our knowledge in PD-L1 testing in lung cancer: the archival sample is ‘promoted’!

The therapeutic approach for the second-line treatment of patients with advanced non-small-cell lung cancer (NSCLC) without actionable mutations has been recently revolutionized by the approval of immune checkpoint inhibitors. Nivolumab, pembrolizumab and atezolizumab improved overall survival (OS) in patients with advanced pretreated NSCLC with both squamous and nonsquamous histology compared with single-agent docetaxel (Table 1) [1–5]. In the studies with nivolumab and atezolizumab, patients were not selected on the basis of programmed death ligand-1 (PD-L1) expression, on the contrary in the study with pembrolizumab (KEYNOTE-010), patients were included only if they were positive for PD-L1 expression [tumor proportion score (TPS) on at least 1% of tumor cells (TCs)] on the basis of a companion diagnostic test [PD-L1 immunohistochemistry (IHC) 22C3 pharmDx assay]. Table 1.Randomized clinical studies with immune checkpoint inhibitors in pretreated patients with advanced non-small-cell lung cancerStudyAuthorPhaseTreatmentPtsOR (%)PFS (months)OS (months)CheckMate 017Brahmer, 2015IIINivolumab versus docetaxel, (squamous)27220 versus 9, P = 0.0083.5 versus 2.8, P < 0.0019.2 versus 6.0, HR: 0.59, P < 0.001CheckMate 057Borghaei, 2015IIINivolumab versus docetaxel, (non-squamous)58219 versus 12, P = 0.022.3 versus 4.2, P = 0.3912.2 versus 9.4, HR: 0.73, P = 0.0015POPLARFehrenbacher, 2016IIAtezolizumab versus docetaxel28715 versus 152.7 versus 3.012.6 versus 9.7, HR: 0.73, P = 0.04OAKRittmeyer, 2017IIIAtezolizumab versus docetaxel85014 versus 132.8 versus 4.0, HR: 0.9513.8 versus 9.6, HR: 0.73, P = 0.0003KEYNOTE 010Herbst, 2016IIIPembrolizumab 2 versus pembrolizumab 10 versus docetaxel103418% (.0005) versus 18% (.00002) versus 9%3.9 (HR 0.88) versus 4.0 (HR 0.79) versus 4.010.4 (HR 0.71) versus 12.7 (HR 0.61) versus 8.5OR, objective response; PFS, progression-free survival; OS, overall survival; HR, hazard ratio; pts, patients.

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