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

Excerpt

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 iodine-refractory 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 RAI-refractory 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-α and -β [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 iodine-refractory DTC who were treated with sunitinib after the failure of first-line sorafenib. …