Thymic malignancies are rare, and options are limited for metastatic disease. Src plays a role in normal thymic epithelial maturation, and its inhibition with the oral compound saracatinib was postulated to be effective in controlling thymic malignancy.Patients with unresectable thymic malignancy were treated with saracatinib 175mg by mouth daily in 28 days cycles with radiographic evaluation at cycle 2 day 1 for safety, then cycle 3 day 1 and every 8 weeks thereafter. Response was evaluated by RECIST 1.0. A two-stage optimal design was used, powered to detect a true response rate of 20%.21 patients were enrolled at two institutions, 12 of them with thymoma, 9 with thymic carcinoma. Thymoma patients received a median of 4.5 cycles and thymic carcinoma patients a median of 1 cycle. There were no responses, so accrual was halted after the first stage per protocol. 9 patients had stable disease beyond the first assessment. Median time to progression was 5.7 months for thymoma patients and 3.6 months for thymic carcinoma patients. Saracatinib was well tolerated.Src inhibition by saracatinib did not produce any radiographic responses, though some patients did experience stable disease. Though negative, this study shows the feasibility of completing a trial in this rare disease, and of accruing reasonably significant numbers of thymic carcinoma patients. More clinical trials are required for this population (NCT00718809).
View details for DOI 10.1016/j.lungcan.2015.04.008
View details for PubMedID 26009269