Selected highlights of the 2019 Pulmonary Pathology Society Biennial Meeting: PD-L1 test harmonization studies

Abstract

Immune checkpoint inhibitors (ICI) including programmed death 1 (PD-1) inhibitors, such as nivolumab and pembrolizumab, or programmed death ligand 1 (PD-L1) inhibitors, such as atezolizumab and durvalumab, have recently emerged in advanced stage lung cancer as new standards of care. They are now indicated in first-line and second-or later-line treatment of metastatic or locally-advanced stage III non-small cell lung cancer (NSCLC), as well as for metastatic small cell lung cancer (SCLC), as single agent immunotherapy or in combination with chemotherapy. Four PD-L1 immunohistochemistry (IHC) assays have been established and validated in randomized trials, each for a specific ICI. They use different primary monoclonal antibodies, platforms and detection systems, as well as different scoring systems to assess PD-L1 expression either by tumor cells (TCs) and/or by infiltrating immune cells (ICs). Most studies have shown a close analytical performance of three of these clinically-validated standardized assays, but their use restricted to dedicated platforms, which are not all available in most laboratories, questions their applicability. In addition, the relative high costs of the assays have led to the development of in-house protocols in many pathology laboratories. Their use in clinical practice to assess the predictive value of PD-L1 expression for prescription of ICI raises the issue of their reliability and their validation as compared to standardized assays. This article discusses the main comparative studies available between LDT and assays, with clear evidence that LDT can reach a performance equivalent to the trial-validated assays. The requirements are an adequate validation as compared to an appropriate standard, and the participation to external quality assurance programs and training programs for PD-L1 IHC assessment for pathologists.

Performance of Different Diagnostic PD-L1 Clones in Head and Neck Squamous Cell Carcinoma

“…Several harmonization studies for the diagnostic detection of PD-L1 expression were performed in different solid cancer entities with most studies focusing on non-small cell lung cancer (12,14,(26)(27)(28)(29)(30). The results of the study presented here are only partially mirrored by investigations in other tumor entities.…”

Progress and prospects of biomarker-based targeted therapy and immune checkpoint inhibitors in advanced gastric cancer

“…The role of PD-L1 as a biomarker has been widely discussed. It seems that the relationship between PD-L1 expression and the response to immunotherapy is definite; yet, what is the appropriate and uniform cutoff value failed to reach a consensus ( 177 ). Cohort I of the KEYNOTE 059 showed that the PD-L1 CPS ≥1 group had a higher ORR than that of the CPS <1 group (15.5% vs. 6.4%) ( 166 ).…”

Biomarkers in Immunotherapy-Based Precision Treatments of Digestive System Tumors

“…Meanwhile, different staining platforms are used to test various antibodies; for example, FDA approved Dako 22C3 pharma Dx PD-L1 as a companion diagnostic for pembrolizumab, and Dako 28-8 and Ventana SP142 PD-L1 was approved as complementary diagnostics for nivolumab and atezolizumab, respectively. To assess the reliability of these approaches and harmonize PD-L1, Lantuejoul et al ( 32 ) analyzed 41 NSCLC surgical specimens via three platforms [Dako, Ventana, and laboratory-developed tests (LDTs) are included], which involved five IHC PD-L1 detections (22C3, 28-8, SP142, SP 263, and E1L3N assays). The staining results in TCs and immune cells (ICs) suggested a high-consistency in 28-8, 22C3, and SP 263, as well as a dynamic change in LDTs.…”