Oncologic strategies and options for the management of metastatic thymic carcinoma.

Abstract

Thymic carcinoma (TC) is a rare, aggressive subset of thymic epithelial tumors (TETs) with a poor prognosis and limited treatment options. Representing approximately 15-20% of TETs, TC is distinct from thymoma in its histopathologic features, lack of paraneoplastic autoimmune syndromes, and more complex genomic landscape. Surgical resection remains the primary modality for early-stage disease, while platinum-based chemotherapy forms the cornerstone of treatment for advanced or unresectable TC. Advancements in targeted therapies have expanded therapeutic options, resulting in improved clinical efficacy, especially in tumors with high angiogenic activity or specific mutations (e.g., Kit). Immune checkpoint blockade (ICB) has shown activity in TC, with response rates around 20%, and is being explored in combination with chemotherapy, anti-angiogenic agents, and CTLA-4 blockade. Combinatorial strategies have demonstrated enhanced response rates but require vigilant management of immune-related adverse events. Novel therapeutic approaches are emerging, including PRMT5 inhibitors in MTAP-deficient tumors, TROP-2-directed antibody-drug conjugates (e.g., sacituzumab govitecan), and chimeric antigen receptor (CAR) T-cell therapies targeting mesothelin. Bispecific agents such as bintrafusp alfa and ivonescimab, which co-target various pathways, offer innovative strategies. Despite these advances, TC remains a challenging malignancy with no standardized treatment algorithm. Collaborative efforts across institutions will be essential to accelerate progress and improve outcomes in this rare disease.