• Sylvie Lantuejoul, Diane Damotte, Véronique Hofman, and Julien Adam.
• Département de Biopathologie, Centre Léon Bérard UNICANCER, Lyon, France.
• J Thorac Dis. 2019 Jan 1; 11 (Suppl 1): S89-S101.

AbstractLung cancer is the leading cause of cancer death worldwide with low response rates to conventional chemotherapy. New promising therapies have emerged based on programmed cell death protein 1 (PD-1) immunity checkpoint inhibitors (ICI), including anti-PD-1, such as nivolumab and pembrolizumab, or programmed death ligand 1 (PD-L1) inhibitors, such as atezolizumab, durvalumab, and avelumab. The prescription of pembrolizumab has been approved by FDA and EMA for advanced stages non-small cell lung carcinoma (NSCLC), restricted for first-line setting to patients whose tumor presents ≥50% of PD-L1 positive tumor cells (TC), and ≥1% for second-line and beyond, leading to consider PD-L1 assay as a companion diagnostic tool for pembrolizumab. Very recently, the EMA has approved durvalumab for the treatment of patients with unresectable stage III NSCLC not progressing after chemoradiotherapy and whose tumors express PD-L1 on ≥1% of TC. Four standardized PD-L1 immunohistochemistry assays have been used in clinical trials; 22C3 and 28-8 PharmDx assays on Dako/Agilent platforms, and SP142 and SP263 assays on Ventana platforms, each test having been developed initially for a specific ICI. They differ in terms of primary monoclonal antibody, platform, detection system and scoring methods with different thresholds of positivity validated in clinical trials. Several studies have shown a close analytical performance of the 22C3, 28-8 and SP263 assays regarding TC staining in NSCLC, with poor concordance with SP142 assay and for immune cells. However, as dedicated platforms are not available in all pathology laboratories and because of the high cost of these assays, laboratory developed tests are widely used in many countries. Their validation must guarantee the same sensitivities and specificities as compared to standardized assays. Overall, PD-L1 test is of great help to select patients who could benefit for ICI and most pathologists have included this test in their daily practice for advanced stages NSCLC, besides ALK and ROS1 IHC.

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