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Review
. 2023 Oct 8;11(10):2722.
doi: 10.3390/biomedicines11102722.

Immunotherapy and Targeted Therapies Efficacy in Thymic Epithelial Tumors: A Systematic Review

Apostolos C Agrafiotis  1   2 , Mariana Brandão  2   3 , Thierry Berghmans  2   3 , Valérie Durieux  2   4 , Christiane Jungels  2   5
Affiliations
Review

Immunotherapy and Targeted Therapies Efficacy in Thymic Epithelial Tumors: A Systematic Review

Apostolos C Agrafiotis et al. Biomedicines. .

Abstract

Background: Thymic epithelial tumors (TET) are rare neoplasms of the anterior mediastinum. Surgery is the mainstay treatment for resectable TET, whereas systemic treatments are reserved for unresectable and metastatic tumors. The development of new treatments, such as immune checkpoint inhibitors (ICI) and targeted therapies, with promising results in other types of solid tumors, has led to the investigation of their potential efficacy in TET. The study of tumor microenvironments (TME) is another field of investigation that has gained the interest of researchers. Taking into account the complex structure of the thymus and its function in the development of immunity, researchers have focused on TME elements that could predict ICI efficacy.

Materials and methods: The primary objective of this systematic review was to investigate the efficacy of ICI in TET. Secondary objectives included the toxicity of ICI, the efficacy of targeted therapies in TET, and the evaluation of the elements of TME that may be predictive factors of ICI efficacy. A literature search was conducted in February 2023 using the Ovid Medline and SciVerse Scopus databases.

Results: 2944 abstracts were retrieved, of which 31 were retained for the systematic review. Five phase II and one retrospective study assessed ICI efficacy. The overall response rate (ORR) varied from 0% to 34%. Median progression-free survival (PFS) ranged from 3.8 to 8.6 months, being lower in thymic carcinoma (TC) (3.8-4.2 months). Median overall survival (OS) ranged from 14.1 to 35.4 months. Treatment-related adverse events occurred in 6.6% to 27.3% of patients. Sixteen studies assessed targeted therapies. The most active molecule was lenvatinib, with 38% ORR in patients with TC while no activity was detected for imatinib, erlotinib plus bevacizumab, and saracatinib. Ten studies assessed TME elements that could predict ICI efficacy. Four studies focused on the tumor-infiltrating immune cells suggesting improved outcomes in patients with TC and high tumor-infiltrating lymphocyte densities. Another study showed that CD8+, CD20+, and CD204+ tumor-infiltrating immune cells in cancer stroma might be prognostic biomarkers in TC. Another study identified the immune-related long non-coding RNAs as a predictor of response to ICI. Tumor mutational burden was identified as a predictive factor of ICI efficacy in one study.

Conclusions: Despite study heterogeneity, this review shows that ICI could be a therapeutic option for selected patients with TET that are not amenable to curative radical treatment after first-line chemotherapy.

Keywords: immunotherapy; targeted therapies; thymic carcinoma; thymoma; tumor microenvironment.

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Conflict of interest statement

Mariana Brandão has the following COIs but none are related to this work: travel grant: Sanofi, Takeda, AstraZeneca; Sanofi speaker fee: Janssen, Takeda, Pfizer, BMS; advisory board: Sanofi, Janssen; Amgen research grants (my institution): Roche/GNE, AstraZeneca, Merck, Boehringer, Merus, Sanofi, Oxford, and iTeos; PI in clinical trials: Roche/GNE, AstraZeneca, Boehringer, Merus, Sanofi. Thierry Berghmans has the following COIs but none are related to this work: Consultancy for InhaTarget; participation in advisory board for Bayer, Janssen, Merck, BMS, Daiichi-Sankyo, Roche; investigator for Pfizer, Merck, Astra Zeneca, Novartis, Peregrine, Amgen, Novocure; travel grant (Takeda). Apostolos C. Agrafiotis, Valérie Durieux and Christiane Jungels do not have COIs to declare.

Figures

Figure 1
Figure 1
PRISMA flowchart demonstrating the search strategy.
See this image and copyright information in PMC

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