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FDA Approval Summary: Pembrolizumab for the Treatment of Patients With Metastatic Non-Small Cell Lung Cancer Whose Tumors Express Programmed Death-Ligand 1

On October 2, 2015, the U.S. Food and Drug Administration (FDA) granted accelerated approval for pembrolizumab, a breakthrough therapy-designated drug, for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express programmed death-ligand 1 (PD-L1), as determin...

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Autores principales: Sul, Joohee, Blumenthal, Gideon M., Jiang, Xiaoping, He, Kun, Keegan, Patricia, Pazdur, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AlphaMed Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861368/
https://www.ncbi.nlm.nih.gov/pubmed/27026676
http://dx.doi.org/10.1634/theoncologist.2015-0498
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author Sul, Joohee
Blumenthal, Gideon M.
Jiang, Xiaoping
He, Kun
Keegan, Patricia
Pazdur, Richard
author_facet Sul, Joohee
Blumenthal, Gideon M.
Jiang, Xiaoping
He, Kun
Keegan, Patricia
Pazdur, Richard
author_sort Sul, Joohee
collection PubMed
description On October 2, 2015, the U.S. Food and Drug Administration (FDA) granted accelerated approval for pembrolizumab, a breakthrough therapy-designated drug, for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express programmed death-ligand 1 (PD-L1), as determined by an FDA-approved test, and who have disease progression on or after platinum-containing chemotherapy or targeted therapy against anaplastic lymphoma kinase or epidermal growth factor receptor, if appropriate. This indication was approved concurrently with the PD-L1 immunohistochemistry 22C3 pharmDx, a companion diagnostic test for patient selection based on PD-L1 tumor expression. The accelerated approval was granted based on durable objective response rate (ORR) and an acceptable toxicity profile demonstrated in a multicenter, open-label trial enrolling 550 patients with metastatic NSCLC. The efficacy population comprised 61 patients with tumors identified as strongly positive for PD-L1, and the confirmed ORR as determined by blinded independent central review was 41% (95% confidence interval: 28.6%, 54.3%); all were partial responses. At the time of the analysis, responses were ongoing in 21 of 25 patients (84%), with 11 patients (44%) having response duration of ≥6 months. The most commonly occurring (≥20%) adverse reactions included fatigue, decreased appetite, dyspnea, and cough. The most frequent (≥2%) serious adverse drug reactions were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. Immune-mediated adverse reactions occurred in 13% of patients and included pneumonitis, colitis, hypophysitis, and thyroid disorders. The accelerated approval regulations describe approval of drugs and biologic products for serious and life-threatening illnesses based on a surrogate endpoint likely to predict clinical benefit. Under these regulations, a confirmatory trial or trials is required to verify and describe the benefit of pembrolizumab for patients with metastatic NSCLC. IMPLICATIONS FOR PRACTICE: This report presents key information on the U.S. Food and Drug Administration (FDA) accelerated approval of pembrolizumab for the treatment of patients with metastatic non-small cell lung cancer whose tumors express programmed death-ligand 1, as determined by an FDA-approved test, and who have disease progression on or after platinum-containing chemotherapy or targeted therapy against anaplastic lymphoma kinase or epidermal growth factor receptor, if appropriate. The report discusses the data supporting the approval decision, specifically highlighting the incorporation of a companion diagnostic in the key study and the optimal dose of pembrolizumab.
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spelling pubmed-48613682016-05-16 FDA Approval Summary: Pembrolizumab for the Treatment of Patients With Metastatic Non-Small Cell Lung Cancer Whose Tumors Express Programmed Death-Ligand 1 Sul, Joohee Blumenthal, Gideon M. Jiang, Xiaoping He, Kun Keegan, Patricia Pazdur, Richard Oncologist Regulatory Issues: FDA On October 2, 2015, the U.S. Food and Drug Administration (FDA) granted accelerated approval for pembrolizumab, a breakthrough therapy-designated drug, for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express programmed death-ligand 1 (PD-L1), as determined by an FDA-approved test, and who have disease progression on or after platinum-containing chemotherapy or targeted therapy against anaplastic lymphoma kinase or epidermal growth factor receptor, if appropriate. This indication was approved concurrently with the PD-L1 immunohistochemistry 22C3 pharmDx, a companion diagnostic test for patient selection based on PD-L1 tumor expression. The accelerated approval was granted based on durable objective response rate (ORR) and an acceptable toxicity profile demonstrated in a multicenter, open-label trial enrolling 550 patients with metastatic NSCLC. The efficacy population comprised 61 patients with tumors identified as strongly positive for PD-L1, and the confirmed ORR as determined by blinded independent central review was 41% (95% confidence interval: 28.6%, 54.3%); all were partial responses. At the time of the analysis, responses were ongoing in 21 of 25 patients (84%), with 11 patients (44%) having response duration of ≥6 months. The most commonly occurring (≥20%) adverse reactions included fatigue, decreased appetite, dyspnea, and cough. The most frequent (≥2%) serious adverse drug reactions were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. Immune-mediated adverse reactions occurred in 13% of patients and included pneumonitis, colitis, hypophysitis, and thyroid disorders. The accelerated approval regulations describe approval of drugs and biologic products for serious and life-threatening illnesses based on a surrogate endpoint likely to predict clinical benefit. Under these regulations, a confirmatory trial or trials is required to verify and describe the benefit of pembrolizumab for patients with metastatic NSCLC. IMPLICATIONS FOR PRACTICE: This report presents key information on the U.S. Food and Drug Administration (FDA) accelerated approval of pembrolizumab for the treatment of patients with metastatic non-small cell lung cancer whose tumors express programmed death-ligand 1, as determined by an FDA-approved test, and who have disease progression on or after platinum-containing chemotherapy or targeted therapy against anaplastic lymphoma kinase or epidermal growth factor receptor, if appropriate. The report discusses the data supporting the approval decision, specifically highlighting the incorporation of a companion diagnostic in the key study and the optimal dose of pembrolizumab. AlphaMed Press 2016-05 2016-03-29 /pmc/articles/PMC4861368/ /pubmed/27026676 http://dx.doi.org/10.1634/theoncologist.2015-0498 Text en ©AlphaMed Press
spellingShingle Regulatory Issues: FDA
Sul, Joohee
Blumenthal, Gideon M.
Jiang, Xiaoping
He, Kun
Keegan, Patricia
Pazdur, Richard
FDA Approval Summary: Pembrolizumab for the Treatment of Patients With Metastatic Non-Small Cell Lung Cancer Whose Tumors Express Programmed Death-Ligand 1
title FDA Approval Summary: Pembrolizumab for the Treatment of Patients With Metastatic Non-Small Cell Lung Cancer Whose Tumors Express Programmed Death-Ligand 1
title_full FDA Approval Summary: Pembrolizumab for the Treatment of Patients With Metastatic Non-Small Cell Lung Cancer Whose Tumors Express Programmed Death-Ligand 1
title_fullStr FDA Approval Summary: Pembrolizumab for the Treatment of Patients With Metastatic Non-Small Cell Lung Cancer Whose Tumors Express Programmed Death-Ligand 1
title_full_unstemmed FDA Approval Summary: Pembrolizumab for the Treatment of Patients With Metastatic Non-Small Cell Lung Cancer Whose Tumors Express Programmed Death-Ligand 1
title_short FDA Approval Summary: Pembrolizumab for the Treatment of Patients With Metastatic Non-Small Cell Lung Cancer Whose Tumors Express Programmed Death-Ligand 1
title_sort fda approval summary: pembrolizumab for the treatment of patients with metastatic non-small cell lung cancer whose tumors express programmed death-ligand 1
topic Regulatory Issues: FDA
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861368/
https://www.ncbi.nlm.nih.gov/pubmed/27026676
http://dx.doi.org/10.1634/theoncologist.2015-0498
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