Thymic malignancies: emerging systemic therapies.

Abstract

The management of thymic malignancies is based on multidisciplinary collaboration. Systemic agents may be administered as an exclusive treatment if local treatment is not achievable. Novel and innovative agents are needed. Integrated genomic analyses reported the activation of targetable signaling pathways in thymomas and thymic carcinomas. Phase II trials reported the antitumor activity of phosphatidylinositol 3-kinase/mechanistic target of rapamycin kinase inhibitors, cyclin dependent kinase inhibitors, and antiangiogenic agents in advanced, refractory thymic malignancies. Meanwhile, a major challenge is the use of immune checkpoint inhibitors, given the frequent association of those tumors with autoimmune disorders. Although those innovative agents were assessed in phase II trials reporting on variable antitumor efficacy in terms of response and survival, in selected and limited cohorts of patients, a better understanding of systemic treatment sequences in a real-life setting is mandatory to analyze the actual efficacy of each line of treatment one after another, define the best clinical-pathological selection of patients for the administration of chemotherapy, targeted agents, and immunotherapy, and develop individualized decision-making to optimize the survival of patients with advanced thymic malignancies.