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RESEARCH PRODUCT

PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis

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// Francesco Passiglia 1, * , Giuseppe Bronte 1, * , Viviana Bazan 1, * , Clara Natoli 2 , Sergio Rizzo 1 , Antonio Galvano 1 , Angela Listi 1 , Giuseppe Cicero 1 , Christian Rolfo 3 , Daniele Santini 4 , Antonio Russo 1 1 Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy 2 Department of Medical, Oral and Biotechnological Sciences, University “G. D’Annunzio”, Chieti, Italy 3 Phase I- Early Clinical Trials Unit, Oncology Department and Multidisciplinary Oncology Center Antwerp (MOCA), Antwerp University Hospital, Edegem, Belgium 4 Medical Oncology Department, Campus Biomedico, University of Rome, Rome, Italy * These authors have contributed equally to this work Correspondence to: Antonio Russo, e-mail: antonio.russo@usa.net Keywords: PD-L1, predictive biomarker, immunotherapy, anti-PD1/PD-L1 MoAbs, NSCLC Received: December 03, 2015     Accepted: February 11, 2016     Published: February 22, 2016 ABSTRACT Background: Clinical trials of immune checkpoints modulators, including both programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors, have recently shown promising activity and tolerable toxicity in pre-treated NSCLC patients. However the predictive role of PD-L1 expression is still controversial. This pooled analysis aims to clarify the association of clinical objective responses to anti PD-1/PD-L1 monoclonal antibodies (MoAbs) and tumor PD-L1 expression in pre-treated NSCLC patients. Methods: Data from published studies, that evaluated efficacy and safety of PD-1/PD-L1 inhibitors in pre-treated NSCLC patients, stratified by tumor PD-L1 expression status (immunohistochemistry, cut-off point 1%), were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference of Lung Cancer, meeting proceedings. Pooled Odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated for the Overall Response Rate (ORR) (as evaluated by Response Evaluation Criteria in Solid Tumors, version 1.1), according to PD-L1 expression status. Results: A total of seven studies, with 914 patients, were eligible. Pooled analysis showed that patients with PD-L1 positive tumors (PD-L1 tumor cell staining ≥1%), had a significantly higher ORR, compared to patients with PD-L1 negative tumors (OR: 2.44; 95% CIs: 1.61-3.68). Conclusions: PD-L1 tumor over-expression seems to be associated with higher clinical activity of anti PD-1/PD-L1 MoAbs, in pre-treated NSCLC patients, suggesting a potential role of PD-L1 expression, IHC cut-off point 1%, as predictive biomarker for the selection of patients to treat with immune-checkpoint inhibitors.