Elsevier

Journal of Thoracic Oncology

Volume 7, Issue 9, September 2012, Pages 1449-1456
Journal of Thoracic Oncology

Original Article
A Phase II Study of Intermittent Sunitinib Malate as Second-Line Therapy in Progressive Malignant Pleural Mesothelioma

https://doi.org/10.1097/JTO.0b013e31825f22eeGet rights and content
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Introduction:

There is no accepted second-line therapy for patients with advanced malignant pleural mesothelioma (MPM), whose disease has progressed after first-line chemotherapy. The multitargeted tyrosine kinase inhibitor sunitinib malate targets several pathways overexpressed in mesothelioma. This phase II study assessed objective response to sunitinib and correlative biomarkers in patients with progressive pretreated MPM.

Methods:

Eligible patients had confirmed MPM, radiological progression after chemotherapy, Eastern Cooperative Oncology Group performance status 0 to 1, and measurable disease. Patients received oral sunitinib 50 mg daily for 28 of every 42 days. The primary endpoint was objective radiological response. Patients without prior pleurodesis had fluorodeoxyglucose positron emission tomographic response assessed by total glycolytic volume criteria. Correlative biomarkers included serum mesothelin, vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, sVEGFR-2, sVEGFR-3, and s-kit.

Results:

Fifty-three patients received sunitinib between July 2006 and December 2009; 51 were assessable for response. Patients received a median of two cycles (range, 1–12); 40% required dose reduction. Fatigue was the most prominent toxicity. Six patients (12%) had a confirmed radiological partial response, 34 (65%) had stable disease, and 11 (22%) had progressive disease as best response. Six of 20 patients had a decrease in fluorodeoxyglucose positron emission tomographic total glycolytic volume of 15% or more. Median overall survival was 6.1 months, and median time to progression was 3.5 months. Correlative biomarkers did not predict treatment response.

Conclusions:

Sunitinib has activity in a subset of patients with pretreated MPM. Consideration should be given to different treatment schedules and examination of other biomarkers for further study of sunitinib in MPM.

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Disclosure: This study was supported in part by a grant from Pfizer Australia Pty Ltd.; partial funding of data management and provision of sunitinib was also supported by the same. The exploratory biomarkers studies were supported by grants from the Sir Charles Gairdner Hospital Research Fund and Pfizer Australia.

None of the authors received support from the tobacco industry for the conduct of this research. The authors declare no conflict of interest.