Immunotherapies for non-small-cell lung cancer and mesothelioma

Our plain-English summary of Immunotherapies for non-small-cell lung cancer and mesothelioma, by A. Thomas, R. Hassan (The Lancet. Oncology, 2012).

The study

• Authors: A. Thomas, R. Hassan
• Journal: The Lancet. Oncology
• Published: 2012;13(7):e301-10
• Type of article: Review
• Cited by: 96 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Non-small-cell lung cancer and mesothelioma are thoracic malignancies, which in their advanced stages are incurable and have poor prognosis. Advances in our understanding of immune responses to tumours, tumour immunosuppression mechanisms, and tumour-specific shared antigens enabled successful early clinical trials of several specific and non-specific immunotherapies. For non-small-cell lung cancer, phase 3 clinical trial results of Toll-like receptor agonists show little promise. However, ongoing phase 3 trials are assessing melanoma-associated antigen A3 vaccine, liposomal BLP25, belagenpumatucel-L, and talactoferrin. In mesothelioma, immunotherapies being investigated include dendritic cell-based and Listeria-based vaccines, and allogeneic tumour cell and WT1 analogue peptide vaccines. Selection of appropriate patients and disease stages for immunotherapy, measurement of tumour-specific immune responses, and understanding the association between immune and clinical responses are some of the major challenges for the development of immunotherapies for these malignancies.

Copyright © 2012 Elsevier Ltd. All rights reserved.

In plain English

This article was a review, not a new study, and it did not study asbestos exposure. The authors searched Medline for English-language reports published between January 1, 1995, and December 15, 2011, on immunotherapy for non-small-cell lung cancer (NSCLC) and mesothelioma. Among the studies reviewed, a phase 1 study gave dendritic cell vaccines to 10 patients with malignant pleural mesothelioma. Three had partial responses, one had stable disease and six had no response, and the measured immune responses did not correlate with clinical responses. In a pilot trial of a WT1 peptide vaccine, the vaccine was safe and six of nine patients tested showed a CD4 T-cell response. In a phase 1 study of the Listeria-based vaccine CRS-207 in 17 patients with advanced cancers, six survived 15 months or more, including one of five patients with mesothelioma. For NSCLC, two phase 3 trials adding PF-3512676 to chemotherapy found similar median survival in treated and control groups, for example 11.0 versus 10.7 months. The authors concluded that measuring immune responses and linking them to clinical responses were major challenges, and that mesothelioma researchers should collaborate to enrol enough patients.

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 of published clinical studies of immunotherapies for NSCLC and mesothelioma
• Who was studied: Published reports found in a Medline search: English-language reports published from January 1, 1995, to December 15, 2011, on immunotherapy in NSCLC and mesothelioma
• Exposure: No asbestos exposure was studied. The exposures reviewed were immunotherapy treatments. For mesothelioma these were dendritic cell-based and Listeria-based vaccines, allogeneic tumour cell vaccines and WT1 analogue peptide vaccines. For NSCLC they included liposomal BLP25, belagenpumatucel-L, MAGE A3 vaccine, immune checkpoint inhibitors, Toll-like receptor agonists, mycobacterial agents and talactoferrin.
• Main results:
  • In a reviewed phase 1 study of dendritic cell vaccination in 10 patients with malignant pleural mesothelioma, three had partial responses, one had stable disease and six had no response.
  • In that same dendritic cell study, the measured immune responses and clinical responses were not correlated.
  • In a reviewed pilot trial of a WT1 analogue peptide vaccine in nine patients, the vaccine was safe, and six of nine patients tested had CD4 T-cell proliferation.
  • In a reviewed phase 1 study of CRS-207 in 17 patients with advanced cancers expressing mesothelin, six of 17 patients survived 15 months or more after the first dose. These six included one of five patients with mesothelioma.
  • In a reviewed phase 3 trial adding PF-3512676 to gemcitabine and cisplatin in NSCLC, median overall survival was 11.0 months (95% CI 9.6 to 12.6) in the intervention group and 10.7 months (9.2 to 12.4) in the control group (p=0.98).
  • In a reviewed phase 2B trial of liposomal BLP25 in stage IIIB or IV NSCLC, median overall survival was 17.2 months in the vaccine group (n=88) versus 13.0 months (HR 0.745, 95% CI 0.533 to 1.042). The review described this difference as not significant.
• The authors' conclusion: The authors concluded that a major challenge is to improve measurement of tumour-specific immune responses and to understand how immune responses relate to clinical responses. They also said that in mesothelioma, a rare malignancy, researchers should collaborate to improve patient accrual for immunotherapy trials.

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: Lung Cancer, Mesothelioma, Prognosis, Clinical Trial, Immunotherapy.

Related studies

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• WT1 peptide vaccinations induce CD4 and CD8 T cell immune responses in patients with mesothelioma and non-small cell lung cancer — L.M. Krug, T. Dao, et al. (2010)
• Mesothelin Immunotherapy for Cancer: Ready for Prime Time? — R. Hassan, A. Thomas, et al. (2016)
• Antitumor activity of type III interferon alone or in combination with type I interferon against human non-small cell lung cancer — H. Fujie, T. Tanaka, et al. (2011)
• Role of Immunotherapy in Small Cell Lung Cancer, Thymic Epithelial Tumors, and Mesothelioma — C.L. Hann, A. Scherpereel, et al. (2019)
• Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors — S. Hendry, R. Salgado, et al. (2017)

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