Title | Everolimus in the treatment of metastatic thymic epithelial tumors. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Hellyer JA, Ouseph MM, Padda SK, Wakelee HA |
Journal | Lung Cancer |
Volume | 149 |
Pagination | 97-102 |
Date Published | 2020 11 |
ISSN | 1872-8332 |
Keywords | Everolimus, Humans, Kelch-Like ECH-Associated Protein 1, Lung Neoplasms, Neoplasms, Glandular and Epithelial, NF-E2-Related Factor 2, Prospective Studies, Retrospective Studies, Thymus Neoplasms |
Abstract | INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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. |
DOI | 10.1016/j.lungcan.2020.09.006 |
Alternate Journal | Lung Cancer |
PubMed ID | 33007678 |
Related Faculty:
Madhu Ouseph, M.D., Ph.D.