Moving Immune Checkpoint Blockade in Thoracic Tumors beyond NSCLC

Our plain-English summary of Moving Immune Checkpoint Blockade in Thoracic Tumors beyond NSCLC, by F. Facchinetti, A. Marabelle, G. Rossi, et al (Journal of Thoracic Oncology, 2016).

The study

• Authors: F. Facchinetti, A. Marabelle, G. Rossi, J.C. Soria, B. Besse, M. Tiseo
• Journal: Journal of Thoracic Oncology
• Published: 2016;11(11):1819-1836
• Type of article: Review
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

SCLC and malignant pleural mesothelioma (MPM) are historically characterized by a disappointing lack of significant therapeutic breakthroughs for novel agents, and both malignancies represent true unmet medical needs. Given the promising results of anti-cytotoxic T-lymphocyte associated protein-4 and anti-programmed cell death-1/programmed death ligand-1 antibodies in the treatment of advanced NSCLCs, these immune checkpoint inhibitors are now also under investigation in SCLC and MPM, as well as in thymic epithelial tumors (TETs). Here, we review the biological and clinical rationale for immune checkpoint inhibition in SCLC, MPM, and TETs and present preliminary clinical results with available antibodies. Immunotherapeutic perspectives for these malignancies in terms of novel agents currently under evaluation or anticipated in the near future are also discussed. Current immune checkpoint blockers targeting cytotoxic T-lymphocyte associated protein-4 and the programmed cell death-1/programmed death ligand-1 axis, administered alone or in combination and as multimodality treatment, are likely to be a valuable addition to the therapeutic array for managing SCLC and MPM; studies in TETs, which are currently in their infancy, are merited. Close attention to potential toxicities will be important to the success of such strategies in these settings.

Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

In plain English

This article is a review, not a new study. The authors reviewed the biological reasoning and early clinical trial results for immune checkpoint inhibitor drugs (antibodies against CTLA-4 and PD-1/PD-L1) in small cell lung cancer, malignant pleural mesothelioma and thymic epithelial tumors. They also listed trials registered on ClinicalTrials.gov as of March 2016. Asbestos appeared only as background: the review described it as the main carcinogenic agent for mesothelioma. Among the mesothelioma trials summarized, the MESO-TREM-2008 trial of tremelimumab in 29 patients did not reach its primary response endpoint. A press release announced that the larger DETERMINE trial of tremelimumab did not meet its primary endpoint of improved overall survival. In an early pembrolizumab trial, 7 of 25 evaluable PD-L1-positive mesothelioma patients had partial responses and 12 had stable disease. With avelumab, 3 of 20 patients (15%) had partial responses. The authors concluded that these drugs had shown valuable activity in small cell lung cancer and mesothelioma, meriting phase III trials, and that close attention to side effects was needed. They noted that much of the data was preliminary.

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: Narrative review of biological rationale and published and preliminary clinical trial results, plus a table of registered ongoing or planned trials
• Who was studied: Published studies and trials in three thoracic cancers: small cell lung cancer, malignant pleural mesothelioma (some trials also included peritoneal mesothelioma), and thymic epithelial tumors. Ongoing trials were taken from ClinicalTrials.gov as of March 31, 2016.
• Exposure: Not an asbestos exposure study. The treatments reviewed were immune checkpoint inhibitor antibodies (ipilimumab, tremelimumab, nivolumab, pembrolizumab, avelumab, durvalumab and others). Asbestos was mentioned only as background, as the main carcinogenic agent for mesothelioma.
• Main results:
  • In the MESO-TREM-2008 trial of tremelimumab (29 patients with advanced mesothelioma progressing after first-line chemotherapy), the primary endpoint was not reached. Median progression-free and overall survival were 6.2 and 10.7 months, and 1- and 2-year survival rates were 48% and 37%.
  • In the MESO-TREM-2012 trial of tremelimumab (29 patients), disease control was obtained in 15 patients (52%).
  • The DETERMINE trial of tremelimumab versus placebo in pleural or peritoneal mesothelioma was reported in a press release not to have met its primary endpoint of improved overall survival.
  • In the KEYNOTE-028 pembrolizumab trial, 38 of 80 screened mesothelioma patients were PD-L1 positive and treated. Among 25 evaluable patients, 7 had partial responses and 12 had stable disease (76% disease control rate).
  • In a phase Ib avelumab cohort of 20 previously treated mesothelioma patients, 3 (15%) had a partial response and 9 (45%) had stable disease.
  • In small cell lung cancer (CheckMate 032), the response rate was 31.1% with nivolumab plus ipilimumab and 12.7% with nivolumab alone.
  • Among 22 thymic carcinoma patients treated with pembrolizumab, two had serious adverse events.
• The authors' conclusion: The authors concluded that CTLA-4 and PD-1/PD-L1 blockers had shown valuable activity in small cell lung cancer and malignant pleural mesothelioma, meriting comparative phase III trials. They also said toxicity, especially with combined blockade, requires attention.
• Limitations the authors state:
  • The authors stated that clinical data in mesothelioma were preliminary.
  • The authors noted that PD-L1 studies used different antibodies and positivity thresholds, making them hard to compare.
  • The authors noted that differences between small cell lung cancer trial results were affected by small sample sizes.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, checkpoint inhibitors.

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• Antibody drug conjugates in thoracic malignancies — J.M. Pacheco, D.R. Camidge (2018)
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• Dual-input tracer kinetic modeling of dynamic contrast-enhanced MRI in thoracic malignancies — S.H. Lee, A. Rimner, et al. (2019)
• Immune checkpoint inhibitor associated reactivation of primary membranous nephropathy responsive to rituximab — J.S. Lin, D.Y. Wang, et al. (2020)

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