Sorafenib in metastatic thyroid cancer: a systematic review

Abstract

Background: Sorafenib was recently approved by the U.S. Food and Drug Administration for radioiodine-resistant metastatic differentiated thyroid cancer (DTC). In addition, two drugs (vandetanib and cabozantinib) have received U.S. Food and Drug Administration approval for use in medullary thyroid cancer (MTC). Several published phase II trials have investigated the efficacy of sorafenib in thyroid cancers, but to date, results from those studies have not been compared.

Methods: A systematic review of the literature was performed to assess response rate, median progression-free survival, and adverse events associated with sorafenib therapy for metastatic thyroid cancers.

Results: This review included seven trials involving 219 patients: 159 with DTC (papillary, follicular, and poorly differentiated), 52 with MTC, and 8 with anaplastic thyroid cancer. No study reported complete responses to treatment. Overall partial response, stable disease, and progressive disease rates were 21%, 60%, and 20%, respectively. The median progression-free survival was 18 months for patients with all subtypes of thyroid cancer. Drug was discontinued in 16% of patients because of toxicities or intolerance, and the dose was reduced in a further 56%. Side effects with an incidence ≥ 50% were hand-foot syndrome (74%), diarrhea (70%), skin rash (67%), fatigue (61%), and weight loss (57%). Deaths not related to progressive disease occurred in nearly 4% of patients.

Conclusion: Treatment with sorafenib in patients with progressive DTC and MTC is a promising strategy, but the adverse event rate is high, leading to a high rate of dose reduction or discontinuation. Consequently, sorafenib use in patients with metastatic thyroid cancer requires careful selection of patients and careful management of side effects.

Keywords: Adverse effects; Chemotherapy; Response rate; Tyrosine kinase inhibitors.

Figure 1.

Forest plot of median progression-free survival for the seven included sorafenib clinical trials (all histologies). The solid lines represent the 95% confidence intervals (CIs). The 95% CIs were unavailable from the papers by Ahmed et al. [20] and Gupta-Abramson et al. [18]. For the studies by Lam et al. [25] and Cabanillas et al [21], the upper limits of 95% CIs for median PFS time were not reached. Consequently, CIs were presented only for the remaining three studies. The overall median PFS (red diamond) for all included trials was 17.9 months (95% CI: 17.9–18). Abbreviation: PFS, progression-free survival.