Oncotarget

Research Papers:

Thymoma Patients Treated in a Phase I Clinic at MD Anderson Cancer Center: Responses to mTOR Inhibitors and Molecular Analyses

Jennifer J. Wheler _, David Hong, Stephen G. Swisher, Gerald S. Falchook, Apostolia Maria Tsimberidou, Thorunn Helgason, Aung Naing, Bettzy Stephen, Filip Janku, Philip J. Stephens, Roman Yelensky and Razelle Kurzrock

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Oncotarget. 2013; 4:890-898. https://doi.org/10.18632/oncotarget.1015

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Abstract

Jennifer Wheler1, David Hong1, Stephen G. Swisher2, Gerald Falchook1, Apostolia M. Tsimberidou1, Thorunn Helgason1, Aung Naing1, Bettzy Stephen1, Filip Janku1, Philip J. Stephens3, Roman Yelensky3, Razelle Kurzrock4

1 Department of Investigational Cancer Therapeutics – a Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center

2 Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center

3 Foundation Medicine, University of California, San Diego

4 Moores Cancer Center, University of California, San Diego

Correspondence:

Jennifer Wheler, email:

Keywords: advanced thymoma, mTOR inhibitors, response, targeted therapy, thymic carcinoma.

Received: May 2, 2013 Accepted: June 9, 2013 Published: June 10, 2013

Abstract

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.


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