Multicenter Randomized Double-Blind Phase III Trial of Donafenib in Progressive Radioactive Iodine-Refractory Differentiated Thyroid Cancer

Abstract

Purpose: The phase II/III study of donafenib was initiated when there was no available treatment indicated for Chinese patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Donafenib, an oral tyrosine kinase inhibitor (TKI), showed good efficacy and tolerability in the phase II study. We aimed to further evaluate the antitumour activity and safety of donafenib in Chinese RAIR-DTC patients. Patients and Methods: This multicenter, double-blind, placebo-controlled, phase III study enrolled 191 patients with progressive RAIR-DTC and randomized in a ratio of 2:1 to donafenib (300 mg twice daily, n=128) or matched placebo (n=63). An open-label donafenib treatment period was allowed upon disease progression. The primary endpoint was progression-free survival (PFS) assessed by the independent review committee. The second endpoints include objective response rate (ORR), disease control rate (DCR), safety, etc. Results: Donafenib demonstrated prolonged median PFS over placebo (12.9 vs. 6.4 months, HR 0.39, 95% CI 0.25-0.61, p<0.0001) in Chinese RAIR-DTC patients. Improved ORR (23.3% vs. 1.7%, p=0.0002) and DCR (93.3% vs. 79.3%,p=0.0044) were observed in the donafenib group over placebo. For donafenib, the most common grade ≥3 treatment-related adverse events included hypertension (13.3%) and hand-foot syndrome (12.5%), 42.2% underwent dose reduction or interruption and 6.3% experienced discontinuation. Conclusions: Donafenib was well-tolerated, and demonstrated clinical benefit in terms of improved PFS, ORR and DCRin patients with RAIR-DTC. The results suggest that donafenib could be a new treatment option for RAIR-DTC patients.

Tyrosine Kinase Inhibitors for Radioactive Iodine Refractory Differentiated Thyroid Cancer

“…More precisely, Donafenib displayed a PFS of 12.9 months compared to 6.4 months for the placebo arm (HR0.39; p < 0.0001). Most common adverse effects were hypertension and palmoplantar erythrodysesthesia [53]. Again, Donafenib has not received FDA or EMA approval.…”

Donafenib as neoadjuvant therapy in locally advanced thyroid cancer: protocol for the DONATHYCA phase II prospective single-arm trial in China

“… 20 Moreover, donafenib prolonged median progression-free survival (PFS) versus placebo (12.9 months vs 6.4 months, p<0.001) in Chinese patients with RAIR-DTC. 21 However, its efficacy in patients with LATC remains unknown. Given that data on neoadjuvant therapy in LATC are extremely limited, this study was planned to investigate the efficacy and safety of donafenib and identify the best possible options for neoadjuvant therapy in LATC.…”