Cabozantinib prolongs progression-free survival (PFS) in patients with previously treated radioiodine-refractory differentiated thyroid cancer (RAIR-DTC), according to updated results from the COSMIC-311 trial published in Cancer

In a prior analysis with 187 patients and a median follow-up of 6.2 months, the median PFS was not reached with cabozantinib and was 1.9 months with placebo (P <.0001). 

In an updated analysis with additional patients and longer follow-up, the median PFS with cabozantinib was nearly 6 times longer than the median PFS with placebo.

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The update of this phase 3 trial ( Identifier: NCT03690388) included 258 patients with RAIR-DTC who had progressed on prior treatment with lenvatinib and/or sorafenib. 

The patients’ median age at baseline was 65 years (range, 31-85). Papillary histology (58%) was more common than follicular histology (44%). In all, 63% of patients had received prior treatment with lenvatinib, 60% had prior sorafenib, and 23% had prior lenvatinib and sorafenib. 

The patients were randomly assigned 2:1 to receive cabozantinib (n=170) or placebo (n=88). Patients assigned to the placebo arm were allowed to cross over to open-label cabozantinib upon radiographic disease progression. 

At a median follow-up of 10.1 months, the median PFS was 11.0 months with cabozantinib and 1.9 months with placebo (hazard ratio [HR], 0.22; 96% CI, 0.15-0.32; P <.0001).

The PFS benefit was seen across subgroups, including patients who had previously received treatment with lenvatinib alone (HR, 0.27; 95% CI, 0.18–0.42), sorafenib alone (HR, 0.19; 95% CI, 0.12–0.30), or both drugs (HR, 0.28; 95% CI, 0.14–0.56).

In addition to improving PFS, cabozantinib improved response. The overall response rate was 11% in patients assigned to cabozantinib and 0% in the placebo arm (P =.0003). 

Eleven percent of patients in both arms received subsequent therapy, not counting crossover. Forty patients in the placebo arm crossed over to receive cabozantinib upon progression.

Despite crossover, there was a trend toward improved overall survival in the cabozantinib arm (HR, 0.76; 95% CI, 0.45-1.31). 

Grade 3-4 treatment-emergent adverse events (TEAEs) occurred in 62% of patients assigned to cabozantinib and 28% of those assigned to placebo. 

The most common grade 3-4 TEAEs (in the cabozantinib and placebo arms, respectively) were hypertension (12% vs 2%), palmar-plantar erythrodysesthesia (10% vs 0%), and fatigue (9% vs 0%). There were no grade 5 treatment-related events. 

“The addition of cabozantinib as a subsequent therapy option should help clinicians to plan and implement sequential treatment with VEGFR TKIs,” the researchers concluded.

Disclosures: This research was supported by Exelixis, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Brose MS, Robinson BG, Sherman SI, et al. Cabozantinib for previously treated radioiodine‐refractory differentiated thyroid cancer: Updated results from the phase 3 COSMIC‐311 trial.Cancer. Published online October 19, 2022. doi:10.1002/cncr.34493