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Thymic epithelial tumors (TETs) are rare tumors of thymic epithelial cells. Treatment options for advanced disease patients who failed standard platinum-based chemotherapy are limited. Phase I and II trials published in the last five years testing new systemic treatments for advanced TET patients are discussed, as well as ongoing trials. A PubMed database literature review was conducted for articles published between January 2016 and December 2021, and ongoing clinical trials were retrieved from ClinicalTrials.gov database. The most promising classes of new drugs in TET patients are angiogenesis inhibitors and immune checkpoint antibodies (ICIs). Sunitinib and Lenvatinib showed response rates of 26% and 38%, respectively, and ICIs showed durable responses in 20–25% in thymic carcinoma (TCs). Both approaches are mainly active in TCs, therefore new treatment options for thymomas are an unmet medical need. Two major new therapeutic strategies are ICI combinations with other drugs and drugs that target pathways that are dysregulated in TETs. Future challenges include the development of preclinical models to help identify novel targets and test new treatment strategies, and randomized clinical trials to provide reliable evidence based on survival endpoints.

Investigational drugs for the treatment of thymic cancer: a focus on phase 1 and 2 clinical trials