Dataset Information

Predictive biomarkers of immunotherapy for non-small cell lung cancer: results from an Experts Panel Meeting of the Italian Association of Thoracic Oncology.

ABSTRACT: Unleashing the potential of immune system to fight cancer has become one of the main promising treatment modalities for advanced non-small cell lung cancer (NSCLC). The knowledge of numerous factors that come into play in the cancer-immunity cycle provide a wide range of potential therapeutic targets, including monoclonal antibodies that inhibits the programmed death-1 (PD-1) checkpoint pathway. Over the last two years, nivolumab, pembrolizumab and atezolizumab received approval for treatment of pretreated advanced NSCLC, and more recently, immunotherapy with pembrolizumab is the new standard of care as first-line in patients with high levels of programmed death-ligand 1 (PD-L1) expression. Selection of patients is mandatory and PD-L1 is the only biomarker currently available in clinical practice. However, PD-L1 staining is an imperfect marker, whose negativity does not exclude a response to immunotherapy, as well as the roughly half of patients are "not-responders" despite high tumor PD-L1 levels. The right cut-off, the differences among various immune checkpoint inhibitors and among various antibody clones, and a not trivial activity reported even in PD-L1 negative tumors are questions still open. New biomarkers beyond to PD-L1 assays as well as new strategies, including combination of immune checkpoint inhibitors are under investigation.

SUBMITTER: Gridelli C

PROVIDER: S-EPMC5504112 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Predictive biomarkers of immunotherapy for non-small cell lung cancer: results from an Experts Panel Meeting of the Italian Association of Thoracic Oncology.

Gridelli Cesare C Ardizzoni Andrea A Barberis Massimo M Cappuzzo Federico F Casaluce Francesca F Danesi Romano R Troncone Giancarlo G De Marinis Filippo F

Translational lung cancer research 20170601 3

Unleashing the potential of immune system to fight cancer has become one of the main promising treatment modalities for advanced non-small cell lung cancer (NSCLC). The knowledge of numerous factors that come into play in the cancer-immunity cycle provide a wide range of potential therapeutic targets, including monoclonal antibodies that inhibits the programmed death-1 (PD-1) checkpoint pathway. Over the last two years, nivolumab, pembrolizumab and atezolizumab received approval for treatment of ...[more]

PMID: 28713682

Similar Datasets

Project description:BackgroundImmunotherapy represents the standard of care in the first-line treatment of advanced non-small-cell lung cancer (NSCLC), either as monotherapy in high programmed death-ligand 1 (PD-L1)-positive tumors (≥50%) or in combination with platinum-based chemotherapy regardless of PD-L1 status. However, most pivotal clinical trials of immune checkpoint inhibitors (ICIs) did not include patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2. Hence, a consensus is lacking on the safety and efficacy of ICIs in this specific subgroup of patients.Materials and methodsA virtual International Expert Panel took place in July 2021 with the aim of reviewing the available evidence on the use of ICIs in NSCLC patients with ECOG PS 2, both in clinical practice and in a research setting.ResultsAll panelists expressed concern about the applicability of currently available PS scales to evaluate patients for ICI treatment. The panelists agreed that, though limited, the available data support the safety of single-agent immunotherapy in PS 2 NSCLC patients, whereas concern was raised on the safety of ICI combinations, mainly related to chemotherapy and/or anti-cytotoxic T-lymphocyte-associated antigen 4 toxicity. On the basis of reviewed data, ICI efficacy may be speculated in PS 2 NSCLC patients; however, PS 2 remains a negative prognostic category as compared to PS 0-1 in patients treated with ICI, as it is for chemotherapy. The panelists defined high, medium and low priorities in clinical research. High priority was attributed to the inclusion of PS 2 patients in prospective clinical trials and the specific evaluation of combined ICI treatments with attenuated chemotherapy doses.ConclusionsBased on the current evidence, the panelists outlined the major limitations affecting PS 2 patients with NSCLC and reached common considerations on the feasibility, safety and effectiveness of ICI monotherapy and ICI combinations in the first-line setting.

Project description:The diagnosis of malignant pleural effusions may be challenging when cytological examination of aspirated pleural fluid is equivocal or noncontributory. The purpose of this study was to identify protein candidate biomarkers differentially expressed in the pleural fluid of patients with mesothelioma, lung adenocarcinoma, lymphoma, and tuberculosis (TB).A multiplex protein biochip comprising 120 biomarkers was used to determine the pleural fluid protein profile of 29 mesotheliomas, 29 lung adenocarcinomas, 12 lymphomas, and 35 tuberculosis. The relative abundance of these predetermined biomarkers among groups served to establish the differential diagnosis of: malignant versus benign (TB) effusions, lung adenocarcinoma versus mesothelioma, and lymphoma versus TB. The selected putative markers were validated using widely available commercial techniques in an independent sample of 102 patients.Significant differences were found in the protein expressions of metalloproteinase-9 (MMP-9), cathepsin-B, C-reactive protein, and chondroitin sulfate between malignant and TB effusions. When integrated into a scoring model, these proteins yielded 85% sensitivity, 100% specificity, and an area under the curve (AUC) of 0.98 for labeling malignancy in the verification sample. For lung adenocarcinoma-mesothelioma discrimination, combining CA19-9, CA15-3, and kallikrein-12 had maximal discriminatory capacity (65% sensitivity, 100% specificity, AUC 0.94); figures which also refer to the validation set. Last, cathepsin-B in isolation was only moderately useful (sensitivity 89%, specificity 62%, AUC 0.75) in separating lymphomatous and TB effusions. However, this last differentiation improved significantly when cathepsin-B was used with respect to the patient's age (sensitivity 72%, specificity 100%, AUC 0.94).In conclusion, panels of 4 (i.e., MMP-9, cathepsin-B, C-reactive protein, chondroitin sulfate), or 3 (i.e., CA19-9, CA15-3, kallikrein-12) different protein biomarkers on pleural fluid samples are highly discriminative for signaling a malignant versus tuberculous effusion, or lung adenocarcinoma versus mesothelioma, respectively. Cathepsin-B could also be helpful in establishing the presence of a lymphomatous effusion versus that of TB, if the patient's age is simultaneously taken into consideration.

Dataset Information

Predictive biomarkers of immunotherapy for non-small cell lung cancer: results from an Experts Panel Meeting of the Italian Association of Thoracic Oncology.

Publications

Predictive biomarkers of immunotherapy for non-small cell lung cancer: results from an Experts Panel Meeting of the Italian Association of Thoracic Oncology.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets