PD-L1 expression in advanced NSCLC: Insights into risk stratification and treatment selection from a systematic literature review. (October 2017)

• Record Type: Journal Article
• Authors: Brody, Robert; Zhang, Yiduo; Ballas, Marc; Siddiqui, Mohd Kashif; Gupta, Palvi; Barker, Craig; Midha, Anita; Walker, Jill
• Is Part Of: Lung cancer. Volume 112(2017)
• Page Start: 200
• Page End: 215
• Publication Date: 2017-10
• Subjects: ALK anaplastic lymphoma kinase -- CI confidence interval -- ECOG The Eastern Cooperative Oncology Group -- DCB durable clinical benefit -- DCR disease control rate -- EGFR epidermal growth factor receptor -- EGFRm+ EGFR mutation positive -- FDA Food and Drug Administration -- FFPE formaldehyde-fixed paraffin-embedded -- HR hazard ratio -- IC immune cell -- IFNγ interferon gamma -- IHC immunohistochemistry -- IRS immunoreactive score -- ISH in-situ hybridization -- min. no. minimum number -- KRAS Kirsten rat sarcoma viral oncogene -- mRNA messenger RNA -- NA not applicable -- NR not reported -- NSCLC non-small cell lung cancer -- ORR objective response rate -- OS overall survival -- PCR polymerase chain reaction -- PD-1 programmed cell death-1 -- PD-L1 programmed cell death ligand-1 -- PFS progression-free survival -- PP percentage positivity -- PS proportion score -- q#w every # weeks -- QIF quantitative immunofluorescence -- ROC receiver operating characteristic -- RR response rate -- SI staining intensity -- TC tumor cell -- TKI tyrosine kinase inhibitor -- TMA tissue microarray -- TTP time to progression -- WHO World Health Organization; PD-L1 -- Checkpoint inhibitors -- Advanced NSCLC -- Immunohistochemistry -- Assay -- Prognosis; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2017.08.005
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: This review examines the utility of PD-L1 as a biomarker in advanced NSCLC. PD-L1 assay variability and lack of standardization hinder cross study comparisons. Limited evidence linking PD-L1 expression to clinicopathologic features in NSCLC. Trend towards poorer prognosis in patients with high vs. low PD-L1 expression. Anti-PD-1/PD-L1 treatment generally has greater benefit in PD-L1 high vs. low NSCLC. Abstract: Tumors can evade immune detection by exploiting inhibitory immune checkpoints such as the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway. Antibodies that block this pathway offer a promising new approach to treatment in advanced/metastatic non-small cell lung cancer (NSCLC). A systematic review of the literature was conducted to assess the association of PD-L1 with important patient and disease characteristics, the prognostic significance of PD-L1 expressing NSCLC tumors, and the value of PD-L1 as a predictive biomarker of response to anti-PD-1/PD-L1 treatments in advanced/metastatic NSCLC. A total of 35 eligible studies were selected for analysis. Methods used to determine PD-L1 in NSCLC tissue varied considerably; with different PD-L1 antibodies, antibody detection methods, and staining cut-offs. Immunohistochemistry was the most frequent type of PD-L1 assay. Overall, study evidence did not support an association between PD-L1 expression and gender, age, smoking history, tumor histology (adenocarcinoma vs. squamous cell carcinoma), performance status, pathologic tumor grade or EGFR/KRAS/ALK mutational status. In several studies, high PD-L1 expression was associated with shorter survival compared with low expression. Most evidence indicated that patients with high vs. low PD-L1 expression were more likely to experience treatment benefit with anti-PD-1/PD-L1 agents (nivolumab, pembrolizumab, durvalumab, atezolizumab, and avelumab) in advanced NSCLC. Variability in the methods used to determine PD-L1 expression in NSCLC tissue suggests a need for standardized use of well-validated PD-L1 diagnostic assays. Although considerable research links PD-L1 expression in tumors to shorter survival in advanced/metastatic NSCLC, its use as a prognostic factor requires more study. As studies of anti-PD-1/PD-L1 agents continue, PD-L1 is likely to play an important role as a predictive biomarker for selecting patients deriving most benefit from anti-PD-1/PD-L1 monotherapy and directing patients with lower levels of tumor PD-L1 expression (with a high unmet medical need), to alternative treatments, such as combination immunotherapies.