Cancer Research, Statistics, and Treatment

: 2021  |  Volume : 4  |  Issue : 4  |  Page : 806-

Cabozantinib for radioiodine-refractory progressive differentiated thyroid cancer

Shuvadeep Ganguly, Ajay Gogia 
 Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
Ajay Gogia
Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi - 110 029

How to cite this article:
Ganguly S, Gogia A. Cabozantinib for radioiodine-refractory progressive differentiated thyroid cancer.Cancer Res Stat Treat 2021;4:806-806

How to cite this URL:
Ganguly S, Gogia A. Cabozantinib for radioiodine-refractory progressive differentiated thyroid cancer. Cancer Res Stat Treat [serial online] 2021 [cited 2022 May 28 ];4:806-806
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Full Text

Treatment options for radioiodine-refractory, differentiated thyroid malignancies that have progressed on sorafenib and/or lenvatinib are limited. Hence, the results of the recently published COSMIC-311 trial, which showed significantly improved progression-free survival with cabozantinib in this subgroup of patients, are promising.[1]

However, certain findings of the trial deserve further analysis. The trial randomized a total of 187 patients, of which the initial 100 patients were evaluated as the objective response rate intention-to-treat (OITT) population. Although it was observed that in the OITT population, 10 (15%) out of 67 patients in the cabozantinib group achieved partial response, in the remaining 87 patients, only 1 patient achieved a partial response resulting in an overall response rate of 1.1%. This discrepancy is surprising. A previous phase II study of cabozantinib in similar settings showed a partial response rate of 40%,[2] whereas in the first-line setting, cabozantinib showed a partial response rate of 54%.[3] This suggests that the response rate of cabozantinib is highly variable. Biomarker-based exploratory analysis, especially of the expression of MET, is required to identify the subgroup of patients who are likely to benefit from the addition of cabozantinib.

It is also worthwhile to note that 21 (34%) of 62 patients in the placebo group also had stable disease. At a median follow-up of 6.2 months, the median progression-free survival of the patients in the placebo group was 1.9 months. However, in a similar placebo cohort of the SELECT study, the median progression-free survival was 3.6 months.[4] This suggests that the biology of differentiated thyroid malignancy is variable, ranging from indolent disease to an aggressive phenotype. A longer follow-up is therefore essential to draw a definitive conclusion regarding the biology of the disease.

Next-generation sequencing is gradually coming to the frontline in the management of thyroid cancers, with the use of targeted agents against BRAF, NTRK, and RET mutations/rearrangements.[5] For patients with radioiodine-refractory, differentiated thyroid cancers, especially those who progress on sorafenib/lenvatinib, it is important to identify such targets to decide further therapy. Only in patients with no actionable genetic mutations/rearrangements, placebo may be considered as the standard of care for the systematic evaluation of any new drug.

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Conflicts of interest

There are no conflicts of interest.


1Brose MS, Robinson B, Sherman SI, Krajewska J, Lin CC, Vaisman F, et al. Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2021;22:1126-38.
2Cabanillas ME, de Souza JA, Geyer S, Wirth LJ, Menefee ME, Liu SV, et al. Cabozantinib as salvage therapy for patients with tyrosine kinase inhibitor-refractory differentiated thyroid cancer: Results of a multicenter phase II international thyroid oncology group trial. J Clin Oncol 2017;35:3315-21.
3Brose MS, Shenoy S, Bhat N, Harlacker AK, Yurtal RK, Posey ZA, et al. A phase II trial of cabozantinib (CABO) for the treatment of radioiodine (RAI)-refractory differentiated thyroid carcinoma (DTC) in the first-line setting. J Clin Oncol 2018;36 Suppl 15:6088.
4Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med 2015;372:621-30.
5Xing M, Haugen BR, Schlumberger M. Progress in molecular-based management of differentiated thyroid cancer. Lancet 2013;381:1058-69.