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
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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)