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
Issued Date
2026-01-01
Resource Type
eISSN
2234943X
Scopus ID
2-s2.0-105033126214
Journal Title
Frontiers in Oncology
Volume
16
Rights Holder(s)
SCOPUS
Bibliographic Citation
Frontiers in Oncology Vol.16 (2026)
Suggested Citation
Brose M.S., Keam B., Krajewska J., Hoff A.O., Vaisman F., Lin C.C., Hitre E., Bowles D.W., Robinson B., Sherman S.I., Ngamphaiboon N., Guo X., Simmons A., Williamson D., Andrianova S., Berry N., Capdevila J. 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. Frontiers in Oncology Vol.16 (2026). doi:10.3389/fonc.2026.1748566 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/115943
Title
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
Author's Affiliation
Universidade de São Paulo
The University of Sydney
The University of Texas MD Anderson Cancer Center
University of Colorado Anschutz School of Medicine
Sidney Kimmel Medical College
National Taiwan University Hospital
Seoul National University Hospital
Ramathibodi Hospital
Instituto Nacional de Cancer
Vall d‘Hebron Institut de Oncologia
Országos Onkológiai Intézet Budapest
Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch
Exelixis, Inc.
The University of Sydney
The University of Texas MD Anderson Cancer Center
University of Colorado Anschutz School of Medicine
Sidney Kimmel Medical College
National Taiwan University Hospital
Seoul National University Hospital
Ramathibodi Hospital
Instituto Nacional de Cancer
Vall d‘Hebron Institut de Oncologia
Országos Onkológiai Intézet Budapest
Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch
Exelixis, Inc.
Corresponding Author(s)
Other Contributor(s)
Abstract
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 BRAF<sup>V600E</sup> 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 BRAF<sup>wt</sup> (wild-type) or BRAF<sup>V600E</sup> 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 BRAF<sup>wt</sup> and 27 had BRAF<sup>V600E</sup>. Cabozantinib prolonged PFS versus placebo in both the BRAF<sup>wt</sup> (hazard ratio [HR] 0.23 [95% CI: 0.12–0.44]; median PFS, 11.1 versus 1.9 months) and BRAF<sup>V600E</sup> (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 BRAF subgroups, objective response rates (ORRs) of 11% and 18% were observed with cabozantinib in the BRAF<sup>wt</sup> and BRAF<sup>V600E</sup>subgroups, respectively. Among patients treated with cabozantinib, 68% of the BRAF<sup>wt</sup> group and 53% of the BRAF<sup>V600E</sup> 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 BRAF mutation status. Thus, cabozantinib is an efficacious treatment option with a manageable safety profile for previously treated patients with RAIR-DTC, including those with BRAF<sup>V600E</sup>.