Thymoma patients treated in a phase I clinic at MD Anderson Cancer Center: responses to mTOR inhibitors and molecular analyses. Oncotarget 2013 Jun;4(6):890-8
Date
06/15/2013Pubmed ID
23765114Pubmed Central ID
PMC3757246DOI
10.18632/oncotarget.1015Scopus ID
2-s2.0-84880780127 (requires institutional sign-in at Scopus site) 38 CitationsAbstract
BACKGROUND: Thymomas and thymic carcinoma are rare tumors with no approved therapies. Our purpose was to analyze the molecular features and outcomes of patients referred to the Clinical Center for Targeted Therapy (Phase I Clinic).
METHODS: We retrospectively reviewed the medical records of consecutive referred patients with advanced/metastatic thymoma or thymic carcinoma
RESULTS: Twenty-one patients were identified (median age 52 years; 10 women; median number of prior systemic therapies = 2). Six of 10 patients (60%) treated with mTOR inhibitor combination regimens achieved stable disease (SD) ≥12 months or a partial response (PR). For patients treated on mTOR inhibitor regimens (N = 10), median time to treatment failure (TTF) was 11.6 months versus 2.3 months on last conventional regimen prior to referral (p=0.024). Molecular analyses (performed by next generation sequencing in seven patients and single polymerase chain reaction (PCR)-based assays in an additional six patients) showed diverse actionable mutations: PIK3CA (1 of 12 tested; 8%); EGFR (1 of 13; 8%); RET (1 of 7; 14%); and AKT1 (1 of 7; 14%). Of two patients with PIK3CA or AKT1 mutations, one was treated with an mTOR inhibitor-based regimen and achieved 26% regression with a TTF of 17 months.
CONCLUSION: Patients with advanced/metastatic thymoma or thymic carcinoma demonstrated prolonged TTF on mTOR inhibitor-based therapy as compared to prior conventional treatment. Heterogeneity in actionable molecular aberrations was observed, suggesting that multi-assay molecular profiling and individualizing treatment merits investigation.
Author List
Wheler J, Hong D, Swisher SG, Falchook G, Tsimberidou AM, Helgason T, Naing A, Stephen B, Janku F, Stephens PJ, Yelensky R, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Female
Humans
Male
Middle Aged
Protein Kinase Inhibitors
Retrospective Studies
Survival Analysis
TOR Serine-Threonine Kinases
Thymoma
United States
