Hostname: page-component-cb9f654ff-5jtmz Total loading time: 0 Render date: 2025-09-03T11:26:45.284Z Has data issue: false hasContentIssue false

Systematic review and meta-analysis of the efficacy of dabrafenib and trametinib in the multi-modal treatment of anaplastic thyroid cancer

Published online by Cambridge University Press:  11 December 2024

Aaron Limonard*
Affiliation:
School of Clinical Medicine, University of Cambridge, Cambridge, UK St John's College, University of Cambridge, Cambridge, UK
James Zhang
Affiliation:
School of Clinical Medicine, University of Cambridge, Cambridge, UK Jesus College, University of Cambridge, Cambridge, UK
James Inchley
Affiliation:
University of Leicester Medical School, Leicester, UK
Audrey Yap
Affiliation:
GKT School of Medicine, King's College London, London, UK
Victor Yan Zhe Lu
Affiliation:
School of Clinical Medicine, University of Cambridge, Cambridge, UK
Neil Tolley
Affiliation:
Imperial College healthcare NHS Trust, London, UK
*
Corresponding author: Aaron Limonard; Email: aaron.limonard@uhs.nhs.uk

Abstract

Objectives

This study analyses the current literature to evaluate the effectiveness of dabrafenib and trametinib in the multi-modal treatment of anaplastic thyroid cancer (ATC).

Method

A systematic review and meta-analysis of the literature were undertaken. The primary endpoint measured was overall response rate (ORR) defined by the RECIST v1.1 guidelines. Secondary endpoints were 12-month overall survival (OS), median OS and progression-free survival (PFS).

Results

Of 656 identified reports, 8 studies were included which featured 95 patients (median age 68.5 years, 46 per cent male). Median follow-up period was 11.8 months with a 12-month OS of 51 per cent. Median OS was 10.4 months. Progression-free survival (PFS) was 6.5 months. The ORR was 71 per cent. A total of 65 patients exhibited a partial or complete response in radiological tumour size. Side effects compared favourably to other kinase inhibitors.

Conclusion

Dabrafenib and trametinib exhibit a promising tumour response with a tolerable side profile. BRAF/MEK inhibitors continue to provide robust responses in BRAF-mutated ATC. The heterogeneity and lack of controls in included studies limits the confidence in the conclusions drawn.

Information

Type
Review Article
Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of J.L.O. (1984) LIMITED

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

Footnotes

Aaron Limonard takes responsibility for the integrity of the content of the paper

References

Molinaro, E, Romei, C, Biagini, A, Sabini, E, Agate, L, Mazzeo, S, et al. Anaplastic thyroid carcinoma: From clinicopathology to genetics and advanced therapies. Nat Rev Endocrinol 2017;13:644–60CrossRefGoogle ScholarPubMed
Pasieka, JL. Anaplastic thyroid cancer. Curr Opin Oncol 2003;15:7883CrossRefGoogle ScholarPubMed
Lowe, NM, Loughran, S, Slevin, NJ, Yap, BK. Anaplastic thyroid cancer: The addition of systemic chemotherapy to radiotherapy led to an observed improvement in survival–A single centre experience and review of the literature. ScientificWorldJournal 2014;2014:674583CrossRefGoogle Scholar
Jannin, A, Escande, A, Al Ghuzlan, A, Blanchard, P, Hartl, D, Chevalier, B, et al. Anaplastic thyroid carcinoma: An update. Cancers (Basel) 2022;14:1061CrossRefGoogle ScholarPubMed
Agosto Salgado, S. Evolution of anaplastic thyroid cancer management: Perspectives in the era of precision oncology. Ther Adv Endocrinol Metab 2021;12:20420188211054692CrossRefGoogle ScholarPubMed
Bible, KC, Kebebew, E, Brierley, J, Brito, JP, Cabanillas, ME, Clark, TJ Jr, et al. 2021 American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid 2021;31:337–86CrossRefGoogle ScholarPubMed
Yau, T, Lo, CY, Epstein, RJ, Lam, AKY, Wan, KY, Lang, BH. Treatment outcomes in anaplastic thyroid carcinoma: Survival improvement in young patients with localized disease treated by combination of surgery and radiotherapy. Ann Surg Oncol 2008;15:2500–5CrossRefGoogle Scholar
Kebebew, E, Greenspan, FS, Clark, OH, Woeber, KA, McMillan, A. Anaplastic thyroid carcinoma. Cancer 2005;103:1330–5CrossRefGoogle ScholarPubMed
Park, JW, Choi, SH, Yoon, HI, Lee, J, Kim, TH, Kim, JW, et al. Treatment outcomes of radiotherapy for anaplastic thyroid cancer. Radiat Oncol J 2018;36:103–13CrossRefGoogle ScholarPubMed
Natoli, C, Perrucci, B, Perrotti, F, Falchi, L, Iacobelli, S; Consorzio Interuniversitario Nazionale per Bio-Oncologia (CINBO). Tyrosine kinase inhibitors. Curr Cancer Drug Targets 2010;10:462–83CrossRefGoogle ScholarPubMed
Pisapia, P, Pepe, F, Iaccarino, A, Sgariglia, R, Nacchio, M, Russo, G, et al. BRAF: A two-faced Janus. Cells 2020;9:2549CrossRefGoogle Scholar
Cheng, Y, Tian, H. Current development status of MEK inhibitors. Molecules 2017;22:1551CrossRefGoogle ScholarPubMed
Research, C. for D.E. and (2022) FDA grants accelerated approval to dabrafenib in combination with trametinib for unresectable or metastatic solid tumors with BRAF V600E mutation. FDA. [online] Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dabrafenib-combination-trametinib-unresectable-or-metastatic-solid.Google Scholar
Eisenhauer, EA, Therasse, P, Bogaerts, J, Schwartz, LH, Sargent, D, Ford, R, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228–47CrossRefGoogle ScholarPubMed
Whiting, PF, Rutjes, AW, Westwood, ME, Mallett, S, Deeks, JJ, Reitsma, JB, et al. QUADAS-2: A revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 2011;155:529–36CrossRefGoogle ScholarPubMed
von Hippel, PT. The heterogeneity statistic I(2) can be biased in small meta-analyses. BMC Med Res Methodol 2015;15:35CrossRefGoogle ScholarPubMed
Subbiah, V, Kreitman, RJ, Wainberg, ZA, Cho, JY, Schellens, JHM, Soria, JC, et al. Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: Updated analysis from the phase II ROAR basket study. Ann Oncol 2022;33:406–15CrossRefGoogle ScholarPubMed
Wang, JR, Zafereo, ME, Dadu, R, Ferrarotto, R, Busaidy, NL, Lu, C, et al. Complete surgical resection following neoadjuvant Dabrafenib plus Trametinib in BRAFV 600E-mutated anaplastic thyroid carcinoma. Thyroid 2019;29:1036–43CrossRefGoogle Scholar
Iyer, PC, Dadu, R, Ferrarotto, R, Busaidy, NL, Habra, MA, Zafereo, M, et al. Real-world experience with targeted therapy for the treatment of anaplastic thyroid carcinoma. Thyroid 2018;29:7987CrossRefGoogle Scholar
Park, J, Jung, HA, Shim, JH, Park, W-Y, Kim, TH, Lee, S-H, et al. Multimodal treatments and outcomes for anaplastic thyroid cancer before and after tyrosine kinase inhibitor therapy: A real-world experience. Eur J Endocrinol 2021;184:837–45CrossRefGoogle ScholarPubMed
Lorimer, C, Cheng, L, Chandler, R, Garcez, K, Gill, V, Graham, K, et al. Dabrafenib and trametinib therapy for advanced anaplastic thyroid cancer - Real-world outcomes from UK centres. Clin Oncol (R Coll Radiol) 2023;35:e60–6CrossRefGoogle ScholarPubMed
Bueno, F, Smulever, A, Califano, I, Guerra, J, Del Grecco, A, Carrera, JM, et al. Dabrafenib plus trametinib treatment in patients with anaplastic thyroid carcinoma: An Argentinian experience. Endocrine 2023;80:134–41CrossRefGoogle ScholarPubMed
Chang, C-F, Yang, M-H, Lee, J-H, Shih, S-R, Lin, C-H, Chen, C-P, et al. The impact of BRAF targeting agents in advanced anaplastic thyroid cancer: A multi-institutional retrospective study in Taiwan. Am J Cancer Res 2022;12:5342–50Google ScholarPubMed
da Silva, TN, Rodrigues, R, Saramago, A, Pires, C, Rito, M, Horta, M, et al. Target therapy for BRAF mutated anaplastic thyroid cancer: A clinical and molecular study. Eur J Endocrinol 2023;188:Ivac011CrossRefGoogle ScholarPubMed
Lin, B, Ma, H, Ma, M, Zhang, Z, Sun, Z, Hsieh, I-Y, et al. The incidence and survival analysis for anaplastic thyroid cancer: A SEER database analysis. Am J Transl Res. 2019;11:5888–96Google ScholarPubMed
Maniakas, A, Dadu, R, Busaidy, NL, Wang, JR, Ferrarotto, R, Lu, C, et al. Evaluation of overall survival in patients with anaplastic thyroid carcinoma, 2000-2019. JAMA Oncol 2020;6:1397–404CrossRefGoogle ScholarPubMed
Gao, X, Hong, C, Xie, Y, Zeng, X. Immunotherapy or targeted therapy: What will be the future treatment for anaplastic thyroid carcinoma? Front Oncol 2023;13:1103147Google ScholarPubMed
Hescheler, DA, Hartmann, MJM, Riemann, B, Michel, M, Bruns, CJ, Alakus, H, et al. Anaplastic thyroid cancer: Genome-based search for new targeted therapy options. Endocr Connect 2022;11:e210624CrossRefGoogle ScholarPubMed
Schadendorf, D, Robert, C, Dummer, R, Flaherty, KT, Tawbi, HA, Menzies, AM, et al. Pyrexia in patients treated with dabrafenib plus trametinib across clinical trials in BRAF-mutant cancers. Eur J Cancer 2021;153:234–41CrossRefGoogle ScholarPubMed
Huang, D, Zhang, J, Zheng, X, Gao, M. Efficacy and safety of Lenvatinib in anaplastic thyroid carcinoma: A meta-analysis. Front Endocrinol (Lausanne) 2022;13:920857CrossRefGoogle ScholarPubMed
Savvides, P, Nagaiah, G, Lavertu, P, Fu, P, Wright, JJ, Chapman, R, et al. Phase II trial of sorafenib in patients with advanced anaplastic carcinoma of the thyroid. Thyroid 2013;23:600–4CrossRefGoogle ScholarPubMed
Bible, KC, Suman, VJ, Menefee, ME, Smallridge, RC, Molina, JR, Maples, WJ, et al. A multiinstitutional phase 2 trial of pazopanib monotherapy in advanced anaplastic thyroid cancer. J Clin Endocrinol Metab 2012;97:3179–84CrossRefGoogle ScholarPubMed
Ravaud, A, de la Fouchardière, C, Caron, P, Doussau, A, Do Cao, C, Asselineau, J, et al. A multicenter phase II study of sunitinib in patients with locally advanced or metastatic differentiated, anaplastic or medullary thyroid carcinomas: Mature data from the THYSU study. Eur J Cancer 2017;76:110–17CrossRefGoogle ScholarPubMed
Robert, C, Grob, JJ, Stroyakovskiy, D, Karaszewska, B, Hauschild, A, Levchenko, E, et al. Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma. N Engl J Med 2019;381:626–36CrossRefGoogle ScholarPubMed
Information about dabrafenib plus trametinib Dabrafenib plus trametinib for treating BRAF V600 mutation-positive advanced non-small-cell lung cancer. In: https://www.nice.org.uk/guidance/TA898/chapter/2-information-about-dabrafenib-plus-trametinib#price [9 August 2023]Google Scholar