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Background: Anti‐programmed cell death 1 antibody is a standard therapy for advanced non‐small cell lung cancer (NSCLC). However, immune‐related adverse events (irAEs), such as skin reactions, are frequently observed. Although skin reactions are associated with clinical efficacy in melanoma, this association in advanced NSCLC and predictors of irAEs remain unclear. Accordingly, this study identified potential correlations of skin reactions with clinical efficacy and clinical predictors of development of skin reactions. Subjects, Materials, and Methods: We retrospectively surveyed patients with advanced NSCLC who received nivolumab or pembrolizumab monotherapy at Sendai Kousei Hospital (n = 155) during January 2016 to April 2018. Treatment efficacy was evaluated in patients with and without skin reactions, and associated predictive markers were determined. A 6‐week landmark analysis was conducted to assess the clinical benefit of early skin reactions. Results: Skin reactions were observed in 51 patients with a median time to onset of 6.4 weeks. The overall response rate (ORR) was significantly higher in patients with skin reactions (57% vs. 19%, p <.001). Median progression‐free survival (PFS) durations of 12.9 and 3.5 months and overall survival durations of not reached and 11.4 months were observed in patients with and without skin reactions, respectively. In the 6‐week landmark analysis, the ORR was significantly higher in patients with skin reactions, and skin reactions were significantly associated with increased PFS. A multivariate analysis identified pre‐existing rheumatoid factor (RF) as an independent predictor of skin reactions. Conclusion: Skin reactions appeared beneficial in patients treated with nivolumab/pembrolizumab for advanced NSCLC and could be predicted by pre‐existing RF. Further large‐scale validations studies are warranted. Implications for Practice: This single‐institutional medical record review that included 155 patients with advanced non‐small cell lung cancer who were treated with nivolumab or pembrolizumab monotherapy revealed that overall response rate and progression‐free survival were significantly better in patients with skin reactions. Pre‐existing rheumatoid factor was an independent predictor of skin reactions. Skin reactions are common immune‐related adverse events associated with PD‐1 therapy. This study investigated the association between the development of skin reactions and clinical benefit of skin reaction, as well as associated predictive markers, in patients with advanced non‐small cell lung cancer who were treated with nivolumab or pembrolizumab monotherapy. [ABSTRACT FROM AUTHOR]

Objective: An association of the programmed cell death-1 (PD-1) and its ligand PD-L1 with various types of malignant tumors has been established. This study aimed to investigate the role of the PD-L1/PD-1 pathway in oral squamous cell carcinoma (OSCC) and oral epithelial precursor lesions (OEPL)., Materials and Methods: We examined 106 OSCC and 79 OEPL specimens for PD-L1 and PD-1 expression by immunohistochemistry. The results were compared with clinicopathological features of OSCC patients., Results: In OSCC and OEPL specimens, PD-L1 expression was detected predominantly in epithelial or carcinoma cells, whereas PD-1 expression was found mainly in infiltrating or stromal lymphocytes. Seventy-two OSCC (67.9%) and 21 OEPL (26.6%) specimens were positive for PD-L1, and 73 OSCC (68.9%) and 23 OEPL (29.2%) specimens were positive for PD-1. PD-L1 and PD-1 expression levels were significantly different between OEPL and OSCC specimens (P < 0.001). There were significant positive correlations between PD-L1 and PD-1 expression in OEPL and OSCC specimens (P < 0.001). PD-L1 and PD-1 immunoreactivity was significantly associated with tumor size (P < 0.05). PD-L1 and PD-1 immunoreactivity in cases with advanced TNM staging was significantly higher than that in low staging cases (P < 0.01). There were significant correlations between PD-L1 and PD-1 expression in OSCC specimens and pathological variables such as stromal lymphocytic reaction (P < 0.05) and invasion depth (P < 0.01)., Conclusion: PD-L1 and PD-1 immunohistochemical status may be related to carcinogenesis, tumor progression, and prognosis in oral epithelial lesions. Agents targeting PD-1 and PD-L1 might be useful for OSCC treatment., (Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)