Efficacy data in 2L DTC CABOMETYX® (cabozantinib) monotherapy
In patients who are RAI-R (or ineligible) and progressed on a prior VEGFR-targeted therapy1
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Meaningful results led to early unblinding in the COSMIC-311 trial2
COSMIC-311 was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial.1,3
2:1 randomization (N=187) RAI-R DTC progressed after prior VEGFR-targeting TKI | ||||
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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 | |||
Post-treatment follow-up§ |
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
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BSC included dose modification and dose interruption. After unblinding, BSC included potentially receiving open-label cabozantinib.1,3
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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.3
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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).2
Multiple primary efficacy outcome measures1
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PFS
- ORR
Stratification factors1
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Age ≤65 years
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Prior lenvatinib
Baseline Characteristics in ITT Population1,3
Total Population | ||
Median age, years (range) ECOG 0 ECOG 1 |
65 (31-85) 46% 54% |
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CABOMETYX | Placebo | |
One previous VEGFR TKI Two previous VEGFR TKIs |
73% (91/125) 27% (34/125) |
77% (48/62) 23% (14/62) |
73% of patients received CABOMETYX after one previous systemic therapy3§
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Updated analysis (N=258).1

CABOMETYX delivered a significant benefit in the primary PFS analysis1
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 (95% CI: 0.14-0.35); P<0.0001.
Early and sustained separation demonstrated at updated analysis -- with a median PFS of 11 months1
Updated analysis

No formal statistical testing was conducted at the time of the updated analysis.
78% reduction in risk of progression or death in both primary and updated analyses
Tumor response observed at the OITT analysis3
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.1,3
CABOMETYX | Placebo | |
ORR, % (95% CI)‖ Stable disease, % (n/N)¶ Disease control rate, % (n/N)** |
15 (7-26) 69 (46/67) 84 (56/67) |
0 (0-11) 42 (14/33) 42 (14/33) |
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P=0.0281; all responses confirmed were partial responses.3
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Stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for PD.5
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Disease control rate was defined as the percentage of patients with a complete response, partial response, or stable disease, as measured by RECIST 1.1.3
76% of patients experienced tumor shrinkage with CABOMETYX at the OITT analysis3††

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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 1.1.3††
- 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 arm3
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Data from OITT analysis of evaluable patients.3
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Confirmed partial response.3

National Comprehensive Cancer Network® (NCCN®)
Cabozantinib (CABOMETYX) has a Category 1 recommendation for patients with RAI-R papillary thyroid cancer that has progressed following VEGFR-targeted therapy§§
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NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
NCCN Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. - §§
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If progression after lenvatinib and/or sorafenib.
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.
References:
- CABOMETYX® (cabozantinib) Prescribing Information. Exelixis, Inc. 2022.
- Exelixis press release. December 21, 2020. https://ir.exelixis.com/news-releases/news-release-details/exelixis-announces-cabozantinib-significantly-improved.
- Brose MS, Robinson B, Sherman SI, et al. Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIS-311): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021;22(8):1126-1138. doi:10.1016/S1470-2045(21)00332-6.
- 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.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Thyroid Cancer V.2.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed May 5, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org.