Research Papers:
PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis
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Abstract
Francesco Passiglia1,*, Giuseppe Bronte1,*, Viviana Bazan1,*, Clara Natoli2, Sergio Rizzo1, Antonio Galvano1, Angela Listì1, Giuseppe Cicero1, Christian Rolfo3, Daniele Santini4, Antonio Russo1
1Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy
2Department of Medical, Oral and Biotechnological Sciences, University “G. D’Annunzio”, Chieti, Italy
3Phase I- Early Clinical Trials Unit, Oncology Department and Multidisciplinary Oncology Center Antwerp (MOCA), Antwerp University Hospital, Edegem, Belgium
4Medical Oncology Department, Campus Biomedico, University of Rome, Rome, Italy
*These authors have contributed equally to this work
Correspondence to:
Antonio Russo, e-mail: [email protected]
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.
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