Do thymic malignancies respond to target therapies?

Interactive CardioVascular and Thoracic Surgery, May 2015

A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was ‘Do thymic malignancies respond to target therapies?’ Altogether, 347 papers were found using the reported search, of which, in our opinion, 16 papers represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. We did not find any randomized controlled trials on target therapies for the thymic malignancies, due to the very small incidence of this tumour, and it seems unlikely that there will be any such trials in the foreseeable future. Three studies on target therapies showed that several cases of thymic malignancies were reported to have partial response (PR) to epidermal growth factor receptor tyrosine kinase inhibitors such as cetuximab and erlotinib, whereas, one study on erlotinib and another on gefitinib showed no activity. Proto-oncogene c-KIT (KIT) mutant thymic carcinomas were noted to benefit from target therapies, implying that systematic sequencing of KIT in thymic carcinoma tumours may be warranted for optimal patient selection. A study that investigated the efficacy of cixutumumab, a fully human IgG1 monoclonal antibody that binds to insulin-like growth factor 1 receptor, indicated that relapsed thymomas tended to respond, whereas thymic carcinoma did not. The antiangiogenesis agent belinostat had modest antitumour activity in heavily pretreated thymoma, but no response to thymic carcinoma was found. Several cases with metastatic thymic carcinoma showed that multitargeted kinase inhibitors, such as sunitinib and sorafenib, were effective. We concluded that, as the side-effects of the agents were tolerable in almost all reported cases, target therapies can be an option for patients with heavily pretreated thymoma.

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Do thymic malignancies respond to target therapies?

Interactive CardioVascular and Thoracic Surgery Do thymic malignancies respond to target therapies? Bin Hu 0 Hao Rong 0 Yongtao Han 0 Qiang Li 0 0 Department of Thoracic Surgery, Sichuan Cancer Hospital and Institute , Chengdu , China A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was 'Do thymic malignancies respond to target therapies?' Altogether, 347 papers were found using the reported search, of which, in our opinion, 16 papers represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. We did not find any randomized controlled trials on target therapies for the thymic malignancies, due to the very small incidence of this tumour, and it seems unlikely that there will be any such trials in the foreseeable future. Three studies on target therapies showed that several cases of thymic malignancies were reported to have partial response (PR) to epidermal growth factor receptor tyrosine kinase inhibitors such as cetuximab and erlotinib, whereas, one study on erlotinib and another on gefitinib showed no activity. Proto-oncogene c-KIT (KIT) mutant thymic carcinomas were noted to benefit from target therapies, implying that systematic sequencing of KIT in thymic carcinoma tumours may be warranted for optimal patient selection. A study that investigated the efficacy of cixutumumab, a fully human IgG1 monoclonal antibody that binds to insulin-like growth factor 1 receptor, indicated that relapsed thymomas tended to respond, whereas thymic carcinoma did not. The antiangiogenesis agent belinostat had modest antitumour activity in heavily pretreated thymoma, but no response to thymic carcinoma was found. Several cases with metastatic thymic carcinoma showed that multitargeted kinase inhibitors, such as sunitinib and sorafenib, were effective. We concluded that, as the side-effects of the agents were tolerable in almost all reported cases, target therapies can be an option for patients with heavily pretreated thymoma. Targeted therapies; Thymic malignancies - INTRODUCTION A best evidence topic was constructed according to a structured protocol. This is fully described in the ICVTS [1]. THREE-PART QUESTION In [ patients with thymoma] does treatment with [targeted therapies] result in [increased survival]? CLINICAL SCENARIO During a national thoracic oncology meeting, a case of heavily pretreated thymoma patient is presented. The patient is considered unable to tolerate additional surgery or chemotherapy. One of the oncologists advises that the patient should be commenced on target therapies to improve survival. You resolve to check the literature yourself. SEARCH STRATEGY We searched Medline from 1950 to March 2014 using the pubmed interface with the search terms [thymoma OR thymic malignancy OR thymic tumour OR thymic carcinoma] AND [sunitinib OR belinostat OR motesanib OR dasatinib OR sorafenib OR imatinib OR cetuximab OR erlotinib OR gefitinib OR target therapy OR targeted therapy]. A total of 347 papers were found using the reported search. Among them, 16 papers were identified that provided the best evidence to answer the question and these papers are presented in Table 1. Target molecular therapy is a new paradigm in the treatment of thymus tumours. Several major signalling pathways with potential targets that have been identified as playing important roles in thymus tumours include the epidermal growth factor receptor (EGFR) inhibitors, cetuximab and erlotinib, the KIT/mast/stem-cell growth factor receptor inhibitors, imatinib and sorafenib, the insulin-like growth factor 1 receptor (IGF-1R) cixutumumab, mammalian target of rapamycin (mTOR) inhibitor, antiangiogenesis pathway inhibitor belinostat and multitargeted kinase inhibitors such as sunitinib, sorafenib and dasatinib. Best evidence papers Two patients with metastatic and chemorefractory thymoma received cetuximab Response and [18F] FDG uptake Both patients achieved PR and reduced [18F] FDG uptake in metastases at 3 months Christodoulou et al. (2008), Ann Oncol, Greece [4] Pedersini et al. (2008), Tumori, Italy [5] Nakagiri et al. (2014), Ann Thorac Cardiovasc Surg, Japan [6] Giaccone et al. (2009), J Thorac Oncol, Netherlands [7] A recurrent patient with metastatic heavily pretreated B2 lymphocytic thymoma received cetuximab A recurrent patient with mixed epithelial cells, lymphocytes stage IV thymoma and severe myasthenia gravis, received erlotinib A patient with heavily pretreated type B3 and stage IVb TC received erlotinib A patient heavily pretreated for a thymoma received gefitinib Seven patients with unresectable B3 (2 patients) thymomas and TC (5 patients) received imatinib A c-KIT mutation (c-KIT exon 11 V560del) patient with hepatic metastatic TC received imatinib A c-KIT mutation (c-KIT exon 11 Y553N missense mut (...truncated)


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Bin Hu, Hao Rong, Yongtao Han, Qiang Li. Do thymic malignancies respond to target therapies?, Interactive CardioVascular and Thoracic Surgery, 2015, pp. 855-859, 20/6, DOI: 10.1093/icvts/ivv040