Epidermal growth factor receptor (EGFR)-targeted therapies in mesothelioma

Our plain-English summary of Epidermal growth factor receptor (EGFR)-targeted therapies in mesothelioma, by P.L. Chia, A.M. Scott, T. John (Expert Opinion on Drug Delivery, 2019).

The study

• Authors: P.L. Chia, A.M. Scott, T. John
• Journal: Expert Opinion on Drug Delivery
• Published: 2019;16(4):441-451
• Type of article: Review
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Malignant mesothelioma (MM) is an aggressive malignancy arising from the mesothelial cells lining the pleura and other serosal membranes. It is associated with an extremely poor prognosis and has limited therapeutic options.

Areas Covered: Epidermal growth factor receptor (EGFR) is known to be highly overexpressed in mesothelioma with reported EGFR overexpression between 44 to 97%. Given this, several anti-EGFR agents have been trialed in mesothelioma. In this review, we provide an overview of the current available data on anti-EGFR therapies in MM and future directions of investigation with these targeted agents in MM.

Expert Opinion: While many anti-EGFR therapies have failed to show significant efficacy in the management of MM, the pathway is biologically active and its abrogation preclinically points toward it being a valid target. Toward targeting the pathway, many novel EGFR-based therapies are still being investigated. Current ongoing research of interest in MM include EGFR-targeted nanotechnology approach for drug delivery, antibodies targeting the extracellular EGFR and potentially anti-EGFR antibody drug conjugates.

In plain English

This article was a review, not a new study. The authors summarized published research on drugs that target the epidermal growth factor receptor (EGFR), a protein on cells, in malignant mesothelioma. They did not study asbestos exposure, which appeared only as background. According to the studies reviewed, EGFR was over-expressed in 44 to 97% of mesothelioma samples. EGFR mutations were extremely rare in pleural mesothelioma (fewer than 10 patients reported), while up to 30% of peritoneal mesothelioma patients were reported to have them. Earlier trials of the drugs gefitinib and erlotinib did not demonstrate clinical efficacy. In a trial adding the antibody cetuximab to chemotherapy, 8 of 18 patients had a partial response, but the study was not continued because a predefined threshold was not reached. In an early trial of an EGFR-targeted treatment called TargomiRs, 1 of 22 assessed patients had a partial response and 15 had stable disease. The authors concluded that approaches used in other cancers had not been useful in mesothelioma, but that targeting EGFR remained a valid strategy.

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 published research and clinical trials on anti-EGFR therapies in malignant mesothelioma (no new patient data)
• Who was studied: No study population of its own; the review covered published laboratory, animal and clinical studies of malignant mesothelioma (pleural and peritoneal)
• Exposure: Not asbestos exposure. The 'exposure' reviewed was treatment with anti-EGFR therapies: tyrosine kinase inhibitors (such as gefitinib and erlotinib), antibodies against EGFR (cetuximab, nimotuzumab), EGFR-targeted TargomiRs, antibody drug conjugates and CAR-T cells. Asbestos was mentioned only as background.
• Main results:
  • Earlier studies cited by the review reported EGFR over-expression in 44 to 97% of mesotheliomas.
  • Per the literature reviewed, EGFR mutations were extremely rare in malignant pleural mesothelioma, with fewer than 10 patients reported.
  • Per the literature reviewed, up to 30% of peritoneal mesothelioma patients were reported to have EGFR mutations.
  • Clinical studies of EGFR tyrosine kinase inhibitors in mesothelioma, cited by the review, did not demonstrate clinical efficacy.
  • In the MesoMab trial of cetuximab plus chemotherapy, cited by the review, 8 of 18 patients (44%) had a partial response. The study was not continued because a predefined threshold was not reached.
  • In a phase 1 trial of TargomiRs, cited by the review, 22 patients were assessed for response. One (5%) had a partial response, 15 (68%) had stable disease and six (27%) had progressive disease.
• The authors' conclusion: The authors concluded that using the same TKI and monoclonal antibody approaches as in other cancers was not useful in mesothelioma. In their view, targeting EGFR remained a valid strategy that needed better understanding of the disease biology.

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: EGFR, Mesothelioma, Malignant Mesothelioma, Mesothelial Cells, Pleura, Prognosis.

Related studies

• Targeted epidermal growth factor receptor therapy in malignant pleural mesothelioma: where do we stand? — V. Agarwal, M.J. Lind, et al. (2011)
• Epidermal growth factor receptor overexpression in malignant pleural mesothelioma: prognostic correlations — O. Rena, L.R. Boldorini, et al. (2011)
• Pulmonary adenocarcinoma with epidermal growth factor receptor-mutations in asbestos exposed non-smokers: A case series — R.L. Kradin, J. Iafrate, et al. (2017)
• Therapeutic antitumor efficacy of anti-epidermal growth factor receptor antibody, cetuximab, against malignant pleural mesothelioma — J. Kurai, H. Chikumi, et al. (2012)
• Malignant pleural mesothelioma and epidermal growth factor receptor (EGF-R). Relationship of EGF-R with histology and survival using fixed paraffin embedded tissue and the F4, monoclonal antibody — H. Dazzi, P.S. Hasleton, et al. (1990)
• Increased epidermal growth factor-receptor protein in a human mesothelial cell line in response to long asbestos fibers — J.C. Pache, Y.M. Janssen, et al. (1998)

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