RESUMEN
PURPOSE: To retrospectively evaluate sorafenib activity and safety in patients with metastatic thymic carcinoma (TC) and to correlate outcome with c-KIT and PDGFR-alpha mutational status. PATIENTS AND METHODS: Patients with metastatic thymic carcinoma treated with sorafenib after at least one prior line of chemotherapy were included. Objective response rate (ORR) and toxicity were evaluated. Analysis of c-KIT and PDGFR-alpha mutational status was performed retrospectively. RESULTS: From October 2007 to August 2011, 5 patients with metastatic thymic carcinoma were evaluated. A median of 8 cycles of sorafenib (range=3-29) were administered. Two patients (40%) displayed a partial response (PR), two patients presented stable disease (SD), while one patient had progression. The median progression-free (PFS) and overall survival were 28 weeks and 92 weeks, respectively. At mutational analysis, only one patient with PR had c-KIT mutation in exon 17 and was successfully treated with sunitinib for 12 months after progression to sorafenib. No PDGFR-alpha mutations were found. CONCLUSION: Sorafenib activity seems independent from the c-KIT and PDGFR-alpha mutational status. After progression, sequence treatment with a different tyrosine kinase inhibitor can be considered. These results are promising and need further confirmation on larger, possibly prospective, series of patients.
Asunto(s)
Mutación , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Proteínas Proto-Oncogénicas c-kit/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Timoma/tratamiento farmacológico , Timoma/genética , Neoplasias del Timo/tratamiento farmacológico , Neoplasias del Timo/genética , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Niacinamida/administración & dosificación , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Sorafenib , Timoma/mortalidad , Timoma/patología , Neoplasias del Timo/mortalidad , Neoplasias del Timo/patología , Resultado del TratamientoRESUMEN
IMPORTANCE OF THE FIELD: Since first reported just over 30 years ago, some progress has been made in our understanding of thymic cancer - an extremely rare cancer - and how to treat it. However, we are far from the ultimate goal of cure for most patients. AREAS COVERED IN THIS REVIEW: This review provides an overview of the thymic gland's development; features of thymic carcinoma, including its molecular characterization, current staging, and treatment guidelines; and progress made to date for treating advanced disease, concluding with future directions and prospects. WHAT THE READER WILL GAIN: As scientists apply new molecular tools to learn more about cancer, we find that even among common cancers, there exist heterogeneous subtypes necessitating different treatment paradigms. Thus, a one-size-fits-all approach to cancer treatment is being displaced with precision medicine to target the 'Achilles heel' of thymic tumors. TAKE HOME MESSAGE: When approaching thymic carcinoma, we must identify the key driving forces to target its context(s) of vulnerability to ensure the greatest impact of treatment for patients with this extremely rare cancer.
Asunto(s)
Timoma/terapia , Neoplasias del Timo/terapia , Antineoplásicos/uso terapéutico , Terapia Biológica , Cisplatino/uso terapéutico , Ensayos Clínicos como Asunto , Terapia Combinada , Femenino , Genes Supresores de Tumor , Humanos , Masculino , Estadificación de Neoplasias , Oncogenes , Terapia Recuperativa , Timoma/genética , Timoma/patología , Timoma/cirugía , Timo/anatomía & histología , Timo/crecimiento & desarrollo , Neoplasias del Timo/genética , Neoplasias del Timo/fisiopatología , Neoplasias del Timo/cirugíaRESUMEN
Metastatic thymic carcinoma is an aggressive neoplasm for which multimodal therapies are often ineffective. We describe here a heavily pretreated patient with advanced thymic carcinoma responsive to multikinases inhibitor BAY 43-9006 (Sorafenib). Of note, a hitherto unreported c-kit missense mutation on exon 17 (D820E) identified in tumor cells seems to explain the clinical response and highlight the key role of molecular analysis in predicting efficacy of targeted therapies even in thymic neoplasms.