Objectives: 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. Materials and methods: Patients with unresectable thymic malignancy were treated with saracatinib 175. mg 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%. Results: 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. Conclusion: 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).
- Src inhibition
- Thymic carcinoma
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cancer Research