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Lancet Oncol. 2015 Feb;16(2):177-86. doi: 10.1016/S1470-2045(14)71181-7. Epub 2015 Jan 13.

Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial.

Author information

1
Thoracic and GI Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
2
Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
3
Department of Hematology and Oncology, Walter Reed National Military Medical Center, Bethesda, MD, USA.
4
Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
5
Division of Hematology/Oncology, Indiana University Medical Center, Indianapolis, IN, USA.
6
Division of Hematology/Oncology, Lombardi Cancer Center, Georgetown University, Washington, DC, USA.
7
Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
8
Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
9
Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
10
Division of Hematology/Oncology, Lombardi Cancer Center, Georgetown University, Washington, DC, USA. Electronic address: gg496@georgetown.edu.

Erratum in

Abstract

BACKGROUND:

No standard treatments are available for advanced thymic epithelial tumours after failure of platinum-based chemotherapy. We investigated the activity of sunitinib, an orally administered tyrosine kinase inhibitor.

METHODS:

Between May 15, 2012, and Oct 2, 2013, we did an open-label phase 2 trial in patients with histologically confirmed chemotherapy-refractory thymic epithelial tumours. Patients were eligible if they had disease progression after at least one previous regimen of platinum-containing chemotherapy, an Eastern Cooperative Oncology Group performance status of two or lower, measurable disease, and adequate organ function. Patients received 50 mg of sunitinib orally once a day, in 6-week cycles (ie, 4 weeks of treatment followed by 2 weeks without treatment), until tumour progression or unacceptable toxic effects arose. The primary endpoint was investigator-assessed best tumour response at any point, which we analysed separately in thymoma and thymic carcinoma cohorts. Patients who had received at least one cycle of treatment and had their disease reassessed were included in the analyses of response. The trial was registered with ClinicalTrials.gov, number NCT01621568.

FINDINGS:

41 patients were enrolled, 25 with thymic carcinoma and 16 with thymoma. One patient with thymic carcinoma was deemed ineligible after enrolment and did not receive protocol treatment. Of patients who received treatment, one individual with thymic carcinoma was not assessable because she died. Median follow-up on trial was 17 months (IQR 14.0-18.4). Of 23 assessable patients with thymic carcinoma, six (26%, 90% CI 12.1-45.3, 95% CI 10.2-48.4) had partial responses, 15 (65%, 95% CI 42.7-83.6) achieved stable disease, and two (9%, 1.1-28.0) had progressive disease. Of 16 patients with thymoma, one (6%, 95% CI 0.2-30.2) had a partial response, 12 (75%, 47.6-92.7) had stable disease, and three (19%, 4.1-45.7) had progressive disease. The most common grade 3 and 4 treatment-related adverse events were lymphocytopenia (eight [20%] of 40 patients), fatigue (eight [20%]), and oral mucositis (eight [20%]). Five (13%) patients had decreases in left-ventricular ejection fraction, of which three (8%) were grade 3 events. Three (8%) patients died during treatment, including one individual who died of cardiac arrest that was possibly treatment-related.

INTERPRETATION:

Sunitinib is active in previously treated patients with thymic carcinoma. Further studies are needed to identify potential biomarkers of activity.

FUNDING:

National Cancer Institute (Cancer Therapy Evaluation Program).

PMID:
25592632
PMCID:
PMC4401497
DOI:
10.1016/S1470-2045(14)71181-7
[Indexed for MEDLINE]
Free PMC Article

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