Second-line sunitinib as a feasible approach for iodine-refractory differentiated thyroid cancer after the failure of first-line sorafenib.

Abstract

About 5 % of patients with differentiated thyroid cancer (DTC) show RAI-refractory disease, thus having a poor prognosis [1, 2]. Tyrosine-kinase inhibitors (TKIs) has represented a revolution in the management of iodinerefractory DTC [3]. Sorafenib has been the most studied TKI in this field, showing encouraging results in several retrospective and phase II studies [4–8]. Effectiveness of sorafenib in RAI-refractory DTC has been definitely demonstrated in the phase III trial DECISION, where a significant improvement of median progression-free survival (PFS) in the treatment group, as compared with placebo, was reported (10.8 vs 5.8 months; HR 0.58, 95 % CI 0.45–0.75, p\ 0.0001) [9]. Following this finding, sorafenib has became the first TKI approved by the US Food and Drug Administration (FDA) for the treatment of RAIrefractory DTC. Given that the study cohort of the DECISION trial included only TKIs-naive patients, sorafenib can be fully considered the first-line systemic therapy for this clinical setting. Nevertheless, sorafenib has some crucial limits. As reported for all TKIs, it is never curative and has a temporally limited effect. Furthermore, sorafenib induced the development of adverse events leading to drug withdrawal in about 20 % of patients [9]. To date, clear indications about management of RAI-refractory DTC patients after the failure of first-line sorafenib are lacking. Sunitinib is a TKI with a pharmacodynamic profile similar to sorafenib, but broader, targeting RET, c-Kit, VEGFR1, -2, PDGFR-a and -b [10]. Despite few studies have been performed so far, sunitinib seems to be effective for the treatment of RAI-refractory DTC [11–14]. Furthermore, several trials of renal cancer have showed that sunitinib was effective in achieving clinical benefit in the majority of patients who experienced the failure of first-line sorafenib [15], even inducing a longer median PFS. Hence, sunitinib may represent a feasible option as salvage treatment after sorafenib failure also in iodine-refractory DTC. Here we report clinical histories of 3 patients (followed at Federico II University, Department of Clinical Medicine and Surgery, Section of Endocrinology, Naples) with iodinerefractory DTC who were treated with sunitinib after the failure of first-line sorafenib.