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

Francesco Passiglia,Antonio Galvano,Antonio Russo,Viviana Bazan,Clara Natoli,Angela Listì,Daniele Santini,Giuseppe Cicero,Giuseppe Bronte,Christian Rolfo,Sergio Rizzo

doi:10.18632/oncotarget.7582

Abstract

BackgroundClinical 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.MethodsData 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.ResultsA 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).ConclusionsPD-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.

Highlights

Cancer immunotherapy is emerging as a very promising therapeutic strategy for several solid tumors, including non-small cell lung cancer (NSCLC)
programmed cell death-ligand 1 (PD-L1) tumor over-expression seems to be associated with higher clinical activity of anti programmed cell death-1 (PD-1)/PD-L1 monoclonal antibodies (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
The KEYNOTE-001 was a modern, large phase I study, including about 500 NSCLC patients treated with Pembrolizumab, which has shown an overall response rates (ORR) of about 20% and an overall survival (OS) of about 12 months in the overall population, even higher among the patients with an increased tumor PD-L1 expression [20]

Summary

Introduction

Cancer immunotherapy is emerging as a very promising therapeutic strategy for several solid tumors, including non-small cell lung cancer (NSCLC). Different immunohistochemistry (IHC) cut-off points, ranging from 1% to 50%, have been used to define the PD-L1 positivity in tumor specimens, the results of the phase III CheckMate 057 study [24] have recently shown that PD-L1 (IHC, cut-off point 1%) significantly correlated with ORR, progression free survival (PFS) and overall survival (OS), in pre-treated NSCLC patients These data suggested PD-L1 at the lowest expression level (IHC, cut-off point 1%) as the best cut-off, allowing to include all patients who may really benefit from these therapies. 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

Results

Conclusion