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Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers

PloS one, 2015-06, Vol.10 (6), p.e0130142-e0130142 [Peer Reviewed Journal]

COPYRIGHT 2015 Public Library of Science ;COPYRIGHT 2015 Public Library of Science ;2015 Carbognin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;2015 Carbognin et al 2015 Carbognin et al ;ISSN: 1932-6203 ;EISSN: 1932-6203 ;DOI: 10.1371/journal.pone.0130142 ;PMID: 26086854

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Title:
Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers
Author: Carbognin, Luisa ; Pilotto, Sara ; Milella, Michele ; Vaccaro, Vanja ; Brunelli, Matteo ; Caliò, Anna ; Cuppone, Federica ; Sperduti, Isabella ; Giannarelli, Diana ; Chilosi, Marco ; Bronte, Vincenzo ; Scarpa, Aldo ; Bria, Emilio ; Tortora, Giampaolo
Santini, Daniele
Subjects: Antibodies ; Antibodies, Monoclonal - therapeutic use ; Antibodies, Monoclonal, Humanized - therapeutic use ; Antineoplastic Agents - therapeutic use ; Apoptosis ; B7-H1 Antigen - genetics ; Biomarkers ; Blood diseases ; Cancer ; Cancer therapies ; Carcinoma, Non-Small-Cell Lung - diagnosis ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Carcinoma, Non-Small-Cell Lung - genetics ; Care and treatment ; Clinical trials ; Confidence intervals ; Gene Expression Regulation, Neoplastic ; Humans ; Immune checkpoint ; Immunotherapy ; Ligands ; Lung - drug effects ; Lung - metabolism ; Lung - pathology ; Lung cancer ; Lung cancer, Non-small cell ; Lung diseases ; Lung Neoplasms - diagnosis ; Lung Neoplasms - drug therapy ; Lung Neoplasms - genetics ; Medical prognosis ; Melanoma ; Melanoma - diagnosis ; Melanoma - drug therapy ; Melanoma - genetics ; Monoclonal antibodies ; Mutation ; Neoplasms - diagnosis ; Neoplasms - drug therapy ; Neoplasms - genetics ; Non-small cell lung cancer ; Non-small cell lung carcinoma ; Oncology ; Pathology ; Patients ; PD-1 protein ; PD-L1 protein ; Prognosis ; Sensitivity analysis ; Solid tumors ; Targeted cancer therapy ; Treatment Outcome ; Tumor cells ; Tumors ; Urogenital Neoplasms - diagnosis ; Urogenital Neoplasms - drug therapy ; Urogenital Neoplasms - genetics ; Urogenital System - drug effects ; Urogenital System - metabolism ; Urogenital System - pathology
Is Part Of: PloS one, 2015-06, Vol.10 (6), p.e0130142-e0130142
Description: The potential predictive role of programmed death-ligand-1 (PD-L1) expression on tumor cells in the context of solid tumor treated with checkpoint inhibitors targeting the PD-1 pathway represents an issue for clinical research. Overall response rate (ORR) was extracted from phase I-III trials investigating nivolumab, pembrolizumab and MPDL3280A for advanced melanoma, non-small cell lung cancer (NSCLC) and genitourinary cancer, and cumulated by adopting a fixed and random-effect model with 95% confidence interval (CI). Interaction test according to tumor PD-L1 was accomplished. A sensitivity analysis according to adopted drug, tumor type, PD-L1 cut-off and treatment line was performed. Twenty trials (1,475 patients) were identified. A significant interaction (p<0.0001) according to tumor PD-L1 expression was found in the overall sample with an ORR of 34.1% (95% CI 27.6-41.3%) in the PD-L1 positive and 19.9% (95% CI 15.4-25.3%) in the PD-L1 negative population. ORR was significantly higher in PD-L1 positive in comparison to PD-L1 negative patients for nivolumab and pembrolizumab, with an absolute difference of 16.4% and 19.5%, respectively. A significant difference in activity of 22.8% and 8.7% according to PD-L1 was found for melanoma and NSCLC, respectively, with no significant difference for genitourinary cancer. Overall, the three antibodies provide a significant differential effect in terms of activity according to PD-L1 expression on tumor cells. The predictive value of PD-L1 on tumor cells seems to be more robust for anti-PD-1 antibody (nivolumab and pembrolizumab), and in the context of advanced melanoma and NSCLC.
Publisher: United States: Public Library of Science
Language: English
Identifier: ISSN: 1932-6203
EISSN: 1932-6203
DOI: 10.1371/journal.pone.0130142
PMID: 26086854
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central
Public Library of Science (PLoS)
ProQuest Central
DOAJ Directory of Open Access Journals

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Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers

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