Meaningful results led to early unblinding in the COSMIC-311 trial3
COSMIC-311 was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial.1,2
RAI-R DTC progressed after prior VEGFR-targeting TKI
|Treatment until disease progression
Eligible placebo patients were allowed to cross over to receive open-label cabozantinib after BIRC-confirmed PD per RECIST 1.1†
|UNBLINDED TRIAL‡||Cabozantinib 60-mg|
The multiple primary efficacy outcome measures assessed ORR in the first 100 patients (OITT) after 6 months of enrollment and PFS in all patients randomly assigned (ITT). Median follow-up was 6.2 months (IQR: 3.4–9.2) for the ITT population and 8.9 months (IQR: 7.1–10.5) for the OITT population. Median duration of treatment exposure in the safety population was 4.4 months (IQR: 2.1-7.3) for the CABOMETYX patients and 2.3 months (IQR: 1.6-5.6) for the placebo group. An updated analysis evaluated a total of 258 randomized patients.1,2
Multiple primary efficacy outcome measures1
Age ≤65 years
Baseline Characteristics in ITT Population1,2
|Median age, years (range)
|One previous VEGFR TKI
Two previous VEGFR TKIs
73% of patients received CABOMETYX after one previous systemic therapy2§
BSC included dose modification and dose interruption. After unblinding, BSC included potentially receiving open-label cabozantinib.1,2
Tumor response and progression were assessed by MRI or CT. Tumor assessments were performed every 8 weeks after randomization for 12 months, then every 12 weeks thereafter.2
An IDMC for COSMIC-311 recommended ending enrollment and unblinding sites and patients based on cabozantinib reducing the risk of disease progression or death by 78% (HR=0.22; 95% CI: 0.14-0.35; P<0.0001).3
Updated analysis (N=258).1
CABOMETYX delivered a significant benefit in the primary PFS analysis1
78% reduction in risk of progression or death in both primary and updated analyses
- Median PFS was not reached in the primary analysis (n=125, 95% CI: 5.7-NE) vs PFS of 1.9 months with placebo (n=62, 95% CI: 1.8-3.6); HR=0.22, P<0.0001
Early and sustained separation demonstrated at updated analysis -- with a median PFS of 11 months1
Tumor response observed at the OITT analysis2
In the COSMIC-311 trial, the overall response rate (ORR) did not reach a prespecified endpoint for statistical significance (critical P value=0.01). Data below cover tumor response information collected, inclusive of ORR.1,2
|ORR, % (95% CI)|
Stable disease, % (n/N)¶
Disease control rate, % (n/N)**
Stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for PD.4
Disease control rate was defined as the percentage of patients with a complete response, partial response, or stable disease, as measured by RECIST 1.1.2
76% of patients experienced tumor shrinkage with CABOMETYX at the OITT analysis2††
Each vertical line represents 1 patient. The plot represents the best percentage change in tumor size from baseline in the evaluable patient population, as determined by the investigators, per RECIST 1.1.2††
- Among patients with baseline and postbaseline target lesion assessment, 44 (76%) of 58 patients with ≥1 postbaseline target lesion assessment in the CABOMETYX arm had a reduction in target lesions compared with 9 (29%) of 31 patients in the placebo arm2
Data from OITT analysis of evaluable patients.2
Confirmed partial response.2
BIRC=blinded independent radiology committee; BSC=best supportive care; CI=confidence interval; CT=computed tomography; ECOG=Eastern Cooperative Oncology Group performance status; HR=hazard ratio; IDMC=independent data-monitoring committee; IQR=interquartile range; ITT=intent to treat; MRI=magnetic resonance imaging; NE=not estimable; OITT=ORR intent to treat; ORR=overall response rate; PD=progressive disease; PFS=progression-free survival; QD=every day; RAI-R=radioactive iodine-refractory; RECIST=Response Evaluation Criteria in Solid Tumors; SoD=sum of diameter; TKI=tyrosine kinase inhibitor; VEGFR=vascular endothelial growth factor receptor.
- CABOMETYX® (cabozantinib) Prescribing Information. Exelixis, Inc, 2021.
- Brose MS, Robinson B, Sherman SI, et al. Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021;22(8):1126-1138. doi.org/10.106/S1470-2045(21)00332-6.
- Exelixis press release. December 21, 2020. https://ir.exelixis.com/news-releases/news-release-details/exelixis-announces-cabozantinib-significantly-improved.
- Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247.