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Sunitinib in metastatic thymic carcinomas: laboratory findings and initial clinical experience
1Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135 Mannheim, Germany. philipp.stroebel@umm.de
Background:
Thymic carcinoma (TC) is a rare aggressive tumour. Median survival with current treatments is only 2 years. Sunitinib is a multi-targeted tyrosine kinase inhibitor that has shown benefit in various other cancers.
Methods:
Laboratory analyses of snap-frozen tumour tissues were performed to detect activation and genetic mutations of receptor tyrosine kinases (RTKs) in TC samples. On the basis of molecular analyses showing activation of multiple RTKs in their tumour, four patients with metastatic TCs refractory to conventional therapies were treated with sunitinib according to standard protocols.
Results:
RTK analysis in three of the patients showed activation of multiple RTKs, including platelet-derived growth factor-beta and vascular endothelial growth factor 3. Mutations of EGFR, c-KIT, KRAS, and BRAF genes were not found. Administration of sunitinib yielded a partial remission (lasting 2 to 18+ months) according to the RECIST criteria in three patients and stable disease with excellent metabolic response in 18F-FDG-PET in another one. The overall survival with sunitinib treatment ranges from 4 to 40+ months. Withdrawal of the drug in one patient prompted rapid tumour progression that could be controlled by re-administration of sunitinib.
Conclusions:
Sunitinib is an active treatment for metastatic TC. A panel of molecular analyses may be warranted for optimal patient selection.
Insights
Sunitinib shows promise in treating metastatic thymic carcinoma (TC), a rare and aggressive cancer. Molecular analysis may help identify patients who will benefit most from this targeted therapy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Thymic carcinoma (TC) is an aggressive malignancy with poor prognosis.
- Current treatments offer limited survival benefits, with a median survival of only two years.
- Sunitinib, a multi-targeted tyrosine kinase inhibitor, has demonstrated efficacy in other cancer types.
Purpose of the Study:
- To evaluate the efficacy of sunitinib in patients with metastatic thymic carcinoma.
- To investigate the role of receptor tyrosine kinase (RTK) activation in TC response to sunitinib.
Main Methods:
- Laboratory analysis of snap-frozen TC tissues to detect RTK activation and mutations.
- Treatment of four metastatic TC patients, refractory to conventional therapies, with sunitinib.
- Assessment of treatment response using RECIST criteria and 18F-FDG-PET imaging.
Main Results:
- RTK analysis revealed activation of multiple RTKs in three patients; common oncogenic mutations were absent.
- Sunitinib treatment resulted in partial remission in three patients and stable disease with metabolic response in one.
- Overall survival ranged from 4 to over 40 months; drug withdrawal led to progression, reversible by re-administration.
Conclusions:
- Sunitinib demonstrates significant activity as a treatment for metastatic thymic carcinoma.
- Molecular profiling, including RTK analysis, is recommended for patient selection to optimize sunitinib therapy.
