# Current Clinical Paradigm and Therapeutic Advancements in Thymic Malignancies: A Narrative Review

## TL;DR

This review discusses the challenges and recent advances in treating rare thymic tumors, focusing on new therapies like immunotherapy and tyrosine kinase inhibitors.

## Contribution

The paper provides a comprehensive overview of the evolving therapeutic landscape for thymic epithelial tumors, emphasizing recent clinical trial results.

## Key findings

- Immunotherapy and tyrosine kinase inhibitors show promise in treating thymic malignancies.
- Hyperthermic intrathoracic chemotherapy is emerging as a novel treatment option.
- The rarity of thymic tumors complicates clinical trial enrollment and drug development.

## Abstract

Thymic malignancies are a rare diverse group of tumors that occur due to dysfunction in thymic cells and are known to have a poor prognosis. The rare nature of this disease and the lack of mutations that can be targeted with inhibitors in this disease subtype have made it difficult to develop new effective drugs. However, more recently, novel classes of drugs such as immunotherapy and tyrosine kinase inhibitors have shown promising results in clinical trials and more drugs are being developed based on novel preclinical findings. Therefore, in this study we review the clinical characteristics of this disease, evaluate the mutations involved, explain the current standard of care, explore drug resistance, and describe in detail the ongoing novel drug results from in-human clinical trials.

Thymic epithelial tumors (TETs) are a diverse group of rare thymic tumors that arise from thymic epithelial cells. The rarity of these tumors has limited therapeutic advancements due to difficulty to enroll patients into Phase II and III clinical trials. Historically surgery, radiotherapy, and chemotherapy have been the mainstay therapeutic options for these patients with the development of new therapeutics hindered by the rarity, histological and molecular heterogeneity, and lack of actionable mutations. However, more recently, innovations in immunotherapy, next-generation tyrosine kinase inhibitors, and hyperthermic intrathoracic chemotherapy (HITHOC) have transformed the therapeutic landscape with more promising therapies currently under investigation. In this review we evaluate the histology and molecular subtypes of TETs, and discuss the therapeutic landscape including the current standard-of-care regimen as well as drugs that are currently in clinical trials.