Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer after prior vascular endothelial growth factor receptor-targeted therapy (COSMIC-311): outcomes by BRAF status.

[BACKGROUND] Cabozantinib is approved for previously treated radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) based on improved progression-free survival (PFS) versus placebo in the COSMIC-311 study. The mutation is common in DTC and is associated with poor prognosis. This planned exploratory analysis of COSMIC-311 reports outcomes by BRAF status.

[METHODS] In this exploratory analysis, outcomes by (wild-type) or status were evaluated in the COSMIC-311 phase 3 study in patients with RAIR-DTC who had previously received lenvatinib and/or sorafenib.

[RESULTS] BRAF status was available for 106 of 258 patients enrolled in COSMIC-311; of these, 74 had and 27 had . Cabozantinib prolonged PFS versus placebo in both the (hazard ratio [HR] 0.23 [95% CI: 0.12-0.44]; median PFS, 11.1 versus 1.9 months) and (HR 0.15 [95% CI: 0.04-0.59]; median PFS, 9.2 versus 1.9 months) subgroups. While no responses were observed with placebo in both subgroups, objective response rates (ORRs) of 11% and 18% were observed with cabozantinib in the and subgroups, respectively. Among patients treated with cabozantinib, 68% of the group and 53% of the group reported grade 3/4 treatment-emergent adverse events; the incidences were 17% and 50% in the corresponding groups treated with placebo.

[CONCLUSIONS] In this subgroup analysis of COSMIC-311, cabozantinib improved PFS and ORR versus placebo irrespective of mutation status. Thus, cabozantinib is an efficacious treatment option with a manageable safety profile for previously treated patients with RAIR-DTC, including those with .