Everolimus in the treatment of metastatic thymic epithelial tumors

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2020-11, Vol.149, p.97-102
• Main Authors: Hellyer, Jessica A., Ouseph, Madhu M., Padda, Sukhmani K., Wakelee, Heather A.
• Format: Article
• Language: English
• Subjects: Everolimus; Next generation sequencing; Thymic carcinoma; Thymoma
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2020.09.006

•Everolimus demonstrated efficacy in a real-world cohort of advanced thymic tumors.•Everolimus has expected and manageable toxicities in patients with thymic tumors.•Pathogenic mutations were found in 27 % of patients and included TP53 and CDKN2A. There is emerging evidence to support the use of mTOR inhibitor everolimus in patients with advanced, relapsed-refractory thymic epithelial tumors (TETs). However, patient selection and identifying predictive biomarkers of response remains a challenge. Here, we describe a single-center experience with everolimus in patients with TETs and provide detailed molecular analysis of their thymic tumors. Data on all patients with advanced TETs who were prescribed everolimus at Stanford University were retrospectively assessed. Time to treatment failure (TTF) and overall survival (OS) were calculated. STAMP, a 130-gene targeted next generation sequencing (NGS) panel, was performed on each tumor sample. Twelve patients with thymoma (T) and three with thymic carcinoma (TC) treated with everolimus were included. Patients had been heavily pre-treated with an average of three prior lines of therapy. Three patients discontinued treatment due to adverse events. The average TTF was 14.7 months in T and 2.6 months in TC with median OS of 27.6 months in the entire cohort (NR T and 5.3 months TC). Two patients with paraneoplastic autoimmune diseases had improvement in autoimmunity on everolimus. Pathogenic mutations were observed in 4/15 (27 %) of patients and includedTP53, KEAP1 and CDKN2A. Several variants of unknown significance in key genes responsible for modulating tumor response to mTOR inhibition were also found. As previously reported in a prospective trial, patients with previously treated advanced TETs appear to benefit from everolimus in this single institution cohort. Moreover, there was a manageable toxicity profile and no cases of everolimus-induced pneumonitis. A targeted NGS panel revealed several pathogenic mutations but there was no association between detectable tumor mutations and time to treatment failure in this cohort.