Marcia S. Brose, B. Keam, Jolanta Krajewska, Ana Oliveira Hoff, Fernanda Vaisman, Chia-Chi Lin, Erika Hitre, Daniel W. Bowles, B. Robinson, Steven I. Sherman, Nuttapong Ngamphaiboon, Xiang Guo, Andrew D. Simmons, Denise Williamson, Svetlana Andrianova, N. Berry, Jaume Capdevila
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 V600E 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 wt (wild-type) or BRAF V600E 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 wt and 27 had BRAF V600E . Cabozantinib prolonged PFS versus placebo in both the BRAF wt (hazard ratio [HR] 0.23 [95% CI: 0.12–0.44]; median PFS, 11.1 versus 1.9 months) and BRAF V600E (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 wt and BRAF V600E subgroups, respectively. Among patients treated with cabozantinib, 68% of the BRAF wt group and 53% of the BRAF V600E 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 V600E .