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Table of Contents
LETTER TO EDITOR
Year : 2022  |  Volume : 5  |  Issue : 1  |  Page : 194-195

Is cabozantinib the common answer to all radioiodine-refractory differentiated thyroid cancers?


1 Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh, India
2 Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India

Date of Submission10-Jan-2022
Date of Decision26-Jan-2022
Date of Acceptance27-Jan-2022
Date of Web Publication31-Mar-2022

Correspondence Address:
Akhil Kapoor
Department of Medical Oncology, Mahamana Pandit Madan Mohan Malviya Cancer Centre and Homi Bhabha Cancer Hospital, Tata Memorial Centre, Varanasi, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/crst.crst_15_22

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How to cite this article:
Kapoor A, Patil VM, Prabhash K. Is cabozantinib the common answer to all radioiodine-refractory differentiated thyroid cancers?. Cancer Res Stat Treat 2022;5:194-5

How to cite this URL:
Kapoor A, Patil VM, Prabhash K. Is cabozantinib the common answer to all radioiodine-refractory differentiated thyroid cancers?. Cancer Res Stat Treat [serial online] 2022 [cited 2022 May 28];5:194-5. Available from: https://www.crstonline.com/text.asp?2022/5/1/194/342446



We read with great interest the article by Brose et al. which was a phase III randomized trial in radioiodine-refractory differentiated thyroid cancer.[1] The approved therapies for this indication are lenvatinib[2] and sorafenib; patients usually progress on these medications within 2 years. After progression on one or both tyrosine kinase inhibitors, no other drug is approved in the absence of any targetable mutation. Of note, mutations in NTRK, BRAF, and RET have been identified in these patients. Taken together, these mutations occur in >50% of papillary thyroid carcinomas and are targetable with available drugs; thus testing for them is of prime importance.[3],[4],[5] Since BRAF[6] and NTRK inhibitors result in response rates >50% with a longer duration of response than that reported with cabozantinib, it seems that cabozantinib should be reserved for cases in which no such targetable mutations are detected.

The study by Brose et al. had a comprehensive statistical plan with two co-primary endpoints: objective response rate (ORR) and progression-free survival (PFS). The endpoint of ORR failed to reach statistical significance (P = 0.028; the preset required P value was below 0.01) but despite this fact, we believe that the results are of clinical importance. There was an ORR of 15% and disease control rate of 84%, as opposed to 0% and 42%, respectively, with placebo. The second co-primary endpoint of PFS met the level of statistical significance with estimates of 57% (96% confidence interval [CI], 43–69) vs. 17% (95% CI, 7–30) at 6 months in the cabozantinib versus placebo arms, respectively. The results for overall survival do not merit comparison due to very limited number of death events. Evaluating the data from the perspective of the European Society of Medical Oncology-magnitude of clinical benefit scale,[7] the study treatment receives a preliminary score of 3, based on the hazard ratio of 0.22 and upgraded score of 4, as cross-over was allowed and the PFS curve showed a plateau. A score of 4 is considered to be practice changing. Thus, cabozantinib adds to our armamentarium for the treatment of radioiodine-refractory differentiated thyroid cancer.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Brose 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.  Back to cited text no. 1
    
2.
Goel A, Singla A. Lenvatinib: A narrative drug review. Cancer Res Stat Treat 2021;4:709-20.  Back to cited text no. 2
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Batra U, Nathany S, Sharma M. NTRK – A narrative review. Cancer Res Stat Treat 2021;4:110-4.  Back to cited text no. 3
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Sharma M, Nathany S, Batra U. BRAF in lung cancer: A narrative review. Cancer Res Stat Treat 2021;4:328-34.  Back to cited text no. 4
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Nathany S, Diwan H, Batra U. RET in non-small cell lung carcinoma: A narrative review. Cancer Res Stat Treat 2021;4:702-8.  Back to cited text no. 5
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Kashyap L, Saha S, Srikanth A. Dabrafenib: A narrative drug review. Cancer Res Stat Treat 2020;3:537-44.  Back to cited text no. 6
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7.
Cherny NI, Dafni U, Bogaerts J, Latino NJ, Pentheroudakis G, Douillard JY, et al. ESMO-Magnitude of Clinical Benefit Scale version 1.1. Ann Oncol 2017;28:2340-66.  Back to cited text no. 7
    




 

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