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Targeted therapy of anaplastic thyroid cancer

https://doi.org/10.17650/2222-1468-2022-12-4-33-38

Abstract

Introduction. Anaplastic thyroid cancer (ATC) is a very rare malignant tumor of the thyroid comprising 1–2 % of all thyroid cancers. In this pathology, response rate for standard systemic therapy is less than 15 %, and long-term results remain unsatisfactory. Additionally, there are no data conclusively showing that cytotoxic chemotherapy improves survival or quality of life in patients with ATC.

Aim. To improve the results of treatment of patients with ATC through evaluation of the effectiveness of targeted therapy in cases of BRAFV600E mutation.

Materials and methods. The multicenter prospective study included 29 patients with ATC IVB–C, T4a–bN1a–bM0–1. The patients were divided into 2 groups. The Group 1 (control) included 15 patients with resectable / nonresectable, metastatic / nonmetastatic ATC (without BRAFV600E mutation), stages IVB–C who received standard types of treatment (surgical intervention, radiation, and chemotherapy). The Group 2 consisted of 14 patients with nonresectable or metastatic ATC, stages IVB–C, who received combination therapy (surgical intervention, radiation, and chemotherapy) with inclusion of inhibitors of BRAF dabrafenib and trametinib in neoadjuvant and adjuvant regimens.

Results. The study showed the effectiveness of targeted therapy with inhibitors of BRAF mutations in treatment of locally advanced non-operable metastatic ATC with BRAFV600E mutation. Overall response (complete response + partial response) in the Group 1 was 0 %, in the Group 2 it was 64 %. Therefore, treatment scheme dabrafenib + trametinib is a prmising approach to combination targeted therapy in patients with ATC and BRAFV600E mutation. C

onclusion. Dabrafenib + trametinib is a promising combination targeted therapy option for patients with ATC with a BRAFV600 mutation demonstrates a high overall response rate, a prolonged duration of response, and an increase in survival rates with controlled toxicity.

About the Authors

P.  A. Nikiforovich
National Medical Research Center of Endocrinology, Ministry of Health of Russia; National Medical Research Center of Radiology, Ministry of Health of Russia
Russian Federation

Petr Alekseevich Nikiforovich

11 Dmitry Ulyanov St., Moscow117292

3 2nd Botkinskij proezd, Moscow 125284



A. P. Polyakov
National Medical Research Center of Radiology, Ministry of Health of Russia
Russian Federation

3 2nd Botkinskij proezd, Moscow 125284



I.   V. Sleptsov
N.I. Pirogov Clinic of High Medical Technologies of the St. Petersburg State University
Russian Federation

154 Fontanka Emb., Saint Petersburg 190103



N.  S. Boyko
N.I. Pirogov Clinic of High Medical Technologies of the St. Petersburg State University
Russian Federation

154 Fontanka Emb., Saint Petersburg 190103



Yu.  A. Gronskaya
N.I. Pirogov Clinic of High Medical Technologies of the St. Petersburg State University
Russian Federation

154 Fontanka Emb., Saint Petersburg 190103



N.   I. Timofeeva
N.I. Pirogov Clinic of High Medical Technologies of the St. Petersburg State University
Russian Federation

154 Fontanka Emb., Saint Petersburg 190103



R.  A. Chernikov
N.I. Pirogov Clinic of High Medical Technologies of the St. Petersburg State University
Russian Federation

154 Fontanka Emb., Saint Petersburg 190103



References

1. Jemal A., Siegel R., Ward E. et al. Cancer Statistics, 2009. CA Cancer J Clin 2009;59(4):1–25. DOI: 10.1002/caac.20073

2. Davies L., Welch H.G. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA 2016;295(18):2164–7. DOI: 10.1001/jama.295.18.2164

3. Besic N., Auersperg M., Us-Krasovec M. et al. Effect of primary treatment on survival in anaplastic thyroid carcinoma. Eur J Surg Oncol 2001;27(3):260–4. DOI: 10.1053/ejso.2000.1098

4. Smallridge R.C., Copland J.A. Anaplastic thyroid carcinoma: pathogenesis and emerging therapies. Clin Oncol 2010;22(6): 486–97. DOI: 10.1016/j.clon.2010.03.013

5. Lee D.Y., Won J.-K., Choi H.S. et al. Recurrence and survival after gross total removal of resectable undifferentiated or poorly differentiated thyroid carcinoma. Thyroid 2016;26(9):1259–68. DOI: 10.1089/thy.2016.0147

6. Pozdeyev N., Gay L.M., Sokol E.S. et al. Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers. Clin Cancer Res 2018;24(13):3059–68. DOI: 10.1158/1078-0432.CCR-18-0373

7. Rao S.N., Zafereo M., Dadu R. et al. Patterns of treatment failure in anaplastic thyroid carcinoma. Thyroid 2017;27(5):672–81. DOI: 10.1089/thy.2016.0395

8. Charles R.P., Silva J., Iezza G. et al. Activating BRAF and PIK3CA mutations cooperate to promote anaplastic thyroid carcinogenesis. Mol Cancer Res 2014;12(7):979–86. DOI: 10.1158/1541-7786.MCR-14-0158-T

9. Hyman D.M., Puzanov I., Subbiah V. et al. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med 2015;373(8):726–36. DOI: 10.1056/nejmoa1502309

10. McFadden D.G., Vernon A., Santiago P.M. et al. p53 constrains progression to anaplastic thyroid carcinoma in a BRAF-mutant mouse model of papillary thyroid cancer. Proc Natl Acad Sci USA 2014;111(16):E1600–9. DOI: 10.1073/pnas.1404357111

11. Long G.V., Stroyakovskiy D., Gogas H. et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med 2014;371(20):1877–88. DOI: 10.1056/nejmoa1406037

12. Nikiforovich P.A., Rumiantsev P.О., Sleptsov I.V. et al. Treatment of BRAFv600e positive anaplastic thyroid carcinoma: case report. Sibirskij onkologicheskij zhurnal = Siberian journal of oncology 2020;19(5):131–44. (In Russ.). DOI: 10.21294/1814-4861-2020-19-5-131-144

13. Bible K.C., Kebebew E., Brierley J. et al. 2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer. Thyroid 2021;31(3):337–86. DOI: 10.1089/thy.2020.0944

14. Long G.V., Flaherty K.T., Stroyakovskiy D. et al. Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study. Ann Oncol 2017;28(7): 1631–9. DOI: 10.1093/annonc/mdx176

15. Smallridge R.C., Marlow L.A., Copland J.A. Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies. Endocr Relat Cancer 2009;16(1):17–44. DOI: 10.1677/ERC-08-0154

16. Wagle N., Van Allen E.M., Treacy D.J. et al. MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. Cancer Discov 2014;4(1):61–8. DOI: 10.1158/2159-8290.CD-13-0631


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For citations:


Nikiforovich P.A., Polyakov A.P., Sleptsov I. ., Boyko N.S., Gronskaya Yu.A., Timofeeva N. ., Chernikov R.A. Targeted therapy of anaplastic thyroid cancer. Head and Neck Tumors (HNT). 2022;12(4):33-38. (In Russ.) https://doi.org/10.17650/2222-1468-2022-12-4-33-38

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ISSN 2222-1468 (Print)
ISSN 2411-4634 (Online)