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

Our plain-English summary of Current Landscape of Immunotherapy Trials Involving the Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Axis in Intrathoracic Tumors, by S.A. Kareff, S. Samtani, M. Burotto, et al (JTO Clinical and Research Reports, 2021).

The study

• Authors: S.A. Kareff, S. Samtani, M. Burotto, V. Prasad, C. Kim
• Journal: JTO Clinical and Research Reports
• Published: 2021;2(4):100149
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

© 2021 The Authors.

In plain English

This article was a review of registered clinical trials. It was not a study of patients or of asbestos exposure. The authors searched the ClinicalTrials.gov registry up to November 13, 2020 for trials of drugs that block the PD-1/PD-L1 immune pathway (anti-PD-(L)1 agents) in four chest cancers: NSCLC, SCLC, mesothelioma and thymic epithelial tumor. They found 686 trials: 540 in NSCLC, 96 in SCLC, 38 in mesothelioma and 12 in thymic epithelial tumor. Twenty-three such drugs were under investigation, and 81% of trials tested combination treatment. For mesothelioma, seven trials were in what the article calls the neoadjuvant adjuvant setting, one was adjuvant, and 30 were in advanced disease. The drugs were most often combined with immunomodulatory therapy (14 trials, 36.8%) and then chemotherapy (9 trials, 23.7%). Of 15 trials launched after an FDA approval for the same use, 14 were randomized, and all compared PD-(L)1-based therapy with chemotherapy alone. The authors concluded that better coordination and innovative trial designs will be vital. They noted that some trials may have been missed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review (cross-sectional analysis) of clinical trials registered on ClinicalTrials.gov
• Who was studied: Therapeutic clinical trials of anti-PD-(L)1 agents posted on ClinicalTrials.gov until November 13, 2020 for NSCLC, SCLC, mesothelioma and thymic epithelial tumor. Trials with unknown, terminated or suspended status were excluded, as were trials including more than one extrathoracic tumor type.
• Exposure: Not an asbestos exposure study. The treatments examined were antibodies and bispecific antibodies targeting PD-1 or PD-L1, used alone or in combination with other treatments.
• Main results:
  • 686 trials were identified: 540 in NSCLC, 96 in SCLC, 38 in mesothelioma and 12 in thymic epithelial tumor.
  • 23 PD-(L)1 agents were under investigation, and 81% of trials assessed combination treatment.
  • Mesothelioma: seven trials were in the neoadjuvant adjuvant setting, one trial tested pembrolizumab in the adjuvant setting, and 30 trials were for advanced mesothelioma.
  • Mesothelioma combination trials: PD-(L)1 inhibitors were most often combined with immunomodulatory therapy (14 trials, 36.8%), then chemotherapy (9 trials, 23.7%).
  • Of 15 trials launched after an FDA approval for a specific indication, 11 (73.3%) were in the People's Republic of China. 14 (93.3%) were randomized, and all compared PD-(L)1-based therapy with chemotherapy alone.
• The authors' conclusion: The authors concluded that greater coordination among stakeholders and adoption of innovative trial designs will be vital to developing effective anti-PD-(L)1 treatment.
• Limitations the authors state:
  • Studies evaluating more than one extrathoracic tumor type were excluded, so some drugs in early development may not have been captured.
  • Only one major registry was searched, so some trials may have been omitted.

Topics

Medical terms in this study, explained in our Lexicon: Immunotherapy, Intrathoracic, Clinical Trial, Mesothelioma, Chemotherapy.

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