Pembrolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives

Ashwin Somasundaram, Timothy F Burns Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA Abstract: Lung cancer is the leading killer of both men and women in the US, and the 5-year survival remains poor. However, the approv...

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Autores principales:	Somasundaram A, Burns TF
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Non-small cell lung cancer programmed death 1 programmed death ligand 1 tumor-infiltrating lymphocytes regulatory T cells. Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1a44d40d230a4cbfab4a5686cc2ef827
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spelling	oai:doaj.org-article:1a44d40d230a4cbfab4a5686cc2ef8272021-12-02T05:09:52ZPembrolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives1179-2728https://doaj.org/article/1a44d40d230a4cbfab4a5686cc2ef8272017-01-01T00:00:00Zhttps://www.dovepress.com/pembrolizumab-in-the-treatment-of-metastatic-non-small-cell-lung-cance-peer-reviewed-article-LCTThttps://doaj.org/toc/1179-2728Ashwin Somasundaram, Timothy F Burns Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA Abstract: Lung cancer is the leading killer of both men and women in the US, and the 5-year survival remains poor. However, the approval of checkpoint blockade immunotherapy has shifted the treatment paradigm and provides hope for improved survival. The ability of non-small-cell lung cancer (NSCLC) to evade the host immune system can be overcome by agents such as pembrolizumab (MK-3475/lambrolizumab), which is a monoclonal antibody targeting the programmed death 1 (PD-1) receptor. In early studies, treatment with pembrolizumab led to dramatic and durable responses in select patients (PD-L1+ tumors). This remarkable efficacy lead to approval of pembrolizumab in the second-line setting as response rates were almost doubled compared to standard of care (SOC) chemotherapy. Most recently, data in the first-line setting from the KEYNOTE-024 study have redefined the SOC therapy for a selected subset of patients. In patients with ≥50% PD-L1+ tumors, pembrolizumab had a clear progression-free survival and overall survival benefit. Toxicity was mostly immune related and similar to checkpoint blockade toxicities observed in previous studies. The initial approval and subsequent studies of pembrolizumab required and utilized a companion diagnostic test, Dako’s IHC 22C3, to assess PD-L1 status of patients. The evaluation and scoring system of this assay has been used by other companies as a reference to develop their own assays, which may complicate selection of patients. Finally, the impact of pembrolizumab in NSCLC is growing as evidenced by the numerous, ongoing trials open for combinations with chemotherapy, chemoradiation, other immunotherapeutics, immunomodulators, tyrosine kinase inhibitors, PI3K inhibitors, MEK inhibitors, hypomethylating agents, and histone deacetylase inhibitors. Further studies are also evaluating pembrolizumab in small-cell lung cancer and malignant pleural mesothelioma. This explosion of studies truly conveys the lack of therapeutic answers for lung cancer patients and the promise of pembrolizumab. Keywords: NSCLC, programmed death 1, programmed death ligand 1, tumor-infiltrating lymphocytes, regulatory T-cellsSomasundaram ABurns TFDove Medical PressarticleNon-small cell lung cancerprogrammed death 1programmed death ligand 1tumor-infiltrating lymphocytesregulatory T cells.Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol Volume 8, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Non-small cell lung cancer programmed death 1 programmed death ligand 1 tumor-infiltrating lymphocytes regulatory T cells. Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Non-small cell lung cancer programmed death 1 programmed death ligand 1 tumor-infiltrating lymphocytes regulatory T cells. Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Somasundaram A Burns TF Pembrolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives
description	Ashwin Somasundaram, Timothy F Burns Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA Abstract: Lung cancer is the leading killer of both men and women in the US, and the 5-year survival remains poor. However, the approval of checkpoint blockade immunotherapy has shifted the treatment paradigm and provides hope for improved survival. The ability of non-small-cell lung cancer (NSCLC) to evade the host immune system can be overcome by agents such as pembrolizumab (MK-3475/lambrolizumab), which is a monoclonal antibody targeting the programmed death 1 (PD-1) receptor. In early studies, treatment with pembrolizumab led to dramatic and durable responses in select patients (PD-L1+ tumors). This remarkable efficacy lead to approval of pembrolizumab in the second-line setting as response rates were almost doubled compared to standard of care (SOC) chemotherapy. Most recently, data in the first-line setting from the KEYNOTE-024 study have redefined the SOC therapy for a selected subset of patients. In patients with ≥50% PD-L1+ tumors, pembrolizumab had a clear progression-free survival and overall survival benefit. Toxicity was mostly immune related and similar to checkpoint blockade toxicities observed in previous studies. The initial approval and subsequent studies of pembrolizumab required and utilized a companion diagnostic test, Dako’s IHC 22C3, to assess PD-L1 status of patients. The evaluation and scoring system of this assay has been used by other companies as a reference to develop their own assays, which may complicate selection of patients. Finally, the impact of pembrolizumab in NSCLC is growing as evidenced by the numerous, ongoing trials open for combinations with chemotherapy, chemoradiation, other immunotherapeutics, immunomodulators, tyrosine kinase inhibitors, PI3K inhibitors, MEK inhibitors, hypomethylating agents, and histone deacetylase inhibitors. Further studies are also evaluating pembrolizumab in small-cell lung cancer and malignant pleural mesothelioma. This explosion of studies truly conveys the lack of therapeutic answers for lung cancer patients and the promise of pembrolizumab. Keywords: NSCLC, programmed death 1, programmed death ligand 1, tumor-infiltrating lymphocytes, regulatory T-cells
format	article
author	Somasundaram A Burns TF
author_facet	Somasundaram A Burns TF
author_sort	Somasundaram A
title	Pembrolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives
title_short	Pembrolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives
title_full	Pembrolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives
title_fullStr	Pembrolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives
title_full_unstemmed	Pembrolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives
title_sort	pembrolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/1a44d40d230a4cbfab4a5686cc2ef827
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Pembrolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives

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