Current Landscape of Immunotherapy Trials Involving the Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Axis in Intrathoracic Tumors

Introduction: The clinical successes seen with anti–programmed cell death protein 1/programmed death-ligand 1 (anti–PD-[L]1) agents have galvanized the field of immuno-oncology. We evaluated the landscape and trends in immunotherapy trials involving the PD-(L)1 axis in intrathoracic tumors. Methods:...

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Main Authors: Samuel A. Kareff, MD, MPH, Suraj Samtani, MD, Mauricio Burotto, MD, MSc, Vinay Prasad, MD, MPH, Chul Kim, MD, MPH
Format: Article
Language:English
Published: Elsevier 2021-04-01
Series:JTO Clinical and Research Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666364321000084
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author Samuel A. Kareff, MD, MPH
Suraj Samtani, MD
Mauricio Burotto, MD, MSc
Vinay Prasad, MD, MPH
Chul Kim, MD, MPH
author_facet Samuel A. Kareff, MD, MPH
Suraj Samtani, MD
Mauricio Burotto, MD, MSc
Vinay Prasad, MD, MPH
Chul Kim, MD, MPH
author_sort Samuel A. Kareff, MD, MPH
collection DOAJ
description Introduction: The clinical successes seen with anti–programmed cell death protein 1/programmed death-ligand 1 (anti–PD-[L]1) agents have galvanized the field of immuno-oncology. We evaluated the landscape and trends in immunotherapy trials involving the PD-(L)1 axis in intrathoracic tumors. Methods: We identified clinical trials involving anti–PD-(L)1 agents on the ClinicalTrials.gov registry through November 13, 2020 for NSCLC, SCLC, mesothelioma, and thymic epithelial tumor. Clinical trials were indexed according to monotherapy versus combination approaches, PD-(L)1 agents under investigation, clinical settings, trial start date, and partner drug(s). We assessed redundancy among the clinical trials. Results: We found 686 clinical trials investigating anti–PD-(L)1 agents for intrathoracic tumors (540 trials in NSCLC, 96 in SCLC, 38 in mesothelioma, and 12 in thymic epithelial tumor). A total of 23 PD-(L)1 inhibitors are undergoing clinical development. A total of 81% of trials assess combination treatment. The number of clinical trials has been growing exponentially in the past decade. PD-(L)1 blockade was frequently combined with chemotherapy or immunomodulatory therapy. Various strategies are in development to overcome resistance to PD-(L)1 blockade in metastatic NSCLC. PD-(L)1 blockade is also increasingly evaluated in neoadjuvant and adjuvant settings. After the U.S. Food and Drug Administration’s approval of an anti–PD-(L)1 agent for a specific indication, 14 trials were launched thereafter, which continued to randomize patients to treatments that were inferior to the best available therapy. Conclusions: The number of clinical trials investigating anti–PD-(L)1 agents in intrathoracic tumors has experienced a steep increase over the past decade with a notable upward trend for combination trials. To reduce duplicative research efforts and accelerate the development of effective immunotherapeutics, improved coordination among key stakeholders and the adoption of innovative trial designs will be vital.
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spelling doaj.art-46856270abe2489faa9c9c8839e9437c2022-12-21T19:45:28ZengElsevierJTO Clinical and Research Reports2666-36432021-04-0124100149Current Landscape of Immunotherapy Trials Involving the Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Axis in Intrathoracic TumorsSamuel A. Kareff, MD, MPH0Suraj Samtani, MD1Mauricio Burotto, MD, MSc2Vinay Prasad, MD, MPH3Chul Kim, MD, MPH4Department of Graduate Medical Education, MedStar Georgetown University Hospital, Washington, District of ColumbiaMedical Oncology Service Bradford Hill, Santiago de Chile, Chile; Intensive Care Unit, Clinica Alemana, Santiago, ChileMedical Oncology Service Bradford Hill, Santiago de Chile, Chile; Medical Oncology Service, Clinica Universidad de los Andes, Las Condes, ChileDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CaliforniaGeorgetown Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, District of Columbia; Corresponding author. Address for correspondence: Chul Kim, MD, MPH, Georgetown Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, 3800 Reservoir Rd. NW, Washington, DC 20007.Introduction: The clinical successes seen with anti–programmed cell death protein 1/programmed death-ligand 1 (anti–PD-[L]1) agents have galvanized the field of immuno-oncology. We evaluated the landscape and trends in immunotherapy trials involving the PD-(L)1 axis in intrathoracic tumors. Methods: We identified clinical trials involving anti–PD-(L)1 agents on the ClinicalTrials.gov registry through November 13, 2020 for NSCLC, SCLC, mesothelioma, and thymic epithelial tumor. Clinical trials were indexed according to monotherapy versus combination approaches, PD-(L)1 agents under investigation, clinical settings, trial start date, and partner drug(s). We assessed redundancy among the clinical trials. Results: We found 686 clinical trials investigating anti–PD-(L)1 agents for intrathoracic tumors (540 trials in NSCLC, 96 in SCLC, 38 in mesothelioma, and 12 in thymic epithelial tumor). A total of 23 PD-(L)1 inhibitors are undergoing clinical development. A total of 81% of trials assess combination treatment. The number of clinical trials has been growing exponentially in the past decade. PD-(L)1 blockade was frequently combined with chemotherapy or immunomodulatory therapy. Various strategies are in development to overcome resistance to PD-(L)1 blockade in metastatic NSCLC. PD-(L)1 blockade is also increasingly evaluated in neoadjuvant and adjuvant settings. After the U.S. Food and Drug Administration’s approval of an anti–PD-(L)1 agent for a specific indication, 14 trials were launched thereafter, which continued to randomize patients to treatments that were inferior to the best available therapy. Conclusions: The number of clinical trials investigating anti–PD-(L)1 agents in intrathoracic tumors has experienced a steep increase over the past decade with a notable upward trend for combination trials. To reduce duplicative research efforts and accelerate the development of effective immunotherapeutics, improved coordination among key stakeholders and the adoption of innovative trial designs will be vital.http://www.sciencedirect.com/science/article/pii/S2666364321000084PD-(L)1 axisNSCLCSCLCMesotheliomaTETImmunotherapy
spellingShingle Samuel A. Kareff, MD, MPH
Suraj Samtani, MD
Mauricio Burotto, MD, MSc
Vinay Prasad, MD, MPH
Chul Kim, MD, MPH
Current Landscape of Immunotherapy Trials Involving the Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Axis in Intrathoracic Tumors
JTO Clinical and Research Reports
PD-(L)1 axis
NSCLC
SCLC
Mesothelioma
TET
Immunotherapy
title Current Landscape of Immunotherapy Trials Involving the Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Axis in Intrathoracic Tumors
title_full Current Landscape of Immunotherapy Trials Involving the Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Axis in Intrathoracic Tumors
title_fullStr Current Landscape of Immunotherapy Trials Involving the Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Axis in Intrathoracic Tumors
title_full_unstemmed Current Landscape of Immunotherapy Trials Involving the Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Axis in Intrathoracic Tumors
title_short Current Landscape of Immunotherapy Trials Involving the Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Axis in Intrathoracic Tumors
title_sort current landscape of immunotherapy trials involving the programmed cell death protein 1 programmed death ligand 1 axis in intrathoracic tumors
topic PD-(L)1 axis
NSCLC
SCLC
Mesothelioma
TET
Immunotherapy
url http://www.sciencedirect.com/science/article/pii/S2666364321000084
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