Sorafenib efficacy in thymic carcinomas seems not to require c-KIT or PDGFR-alpha mutations

Abstract

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.

Keywords: PDGFR alpha; Thymic carcinoma; c-KIT; sorafenib; tyrosine kinase.