Phase 2 study evaluating the combination of sorafenib and temsirolimus in the treatment of radioactive iodine-refractory thyroid cancer Journal Article


Authors: Sherman, E. J.; Dunn, L. A.; Ho, A. L.; Baxi, S. S.; Ghossein, R. A.; Fury, M. G.; Haque, S.; Sima, C. S.; Cullen, G.; Fagin, J. A.; Pfister, D. G.
Article Title: Phase 2 study evaluating the combination of sorafenib and temsirolimus in the treatment of radioactive iodine-refractory thyroid cancer
Abstract: BACKGROUND: Patients with recurrent and/or metastatic, radioactive iodine-refractory thyroid carcinoma have limited treatment options. Sorafenib, an oral kinase inhibitor, is approved by the US Food and Drug Administration for the treatment of radioactive iodine-refractory thyroid carcinoma, although it demonstrated low response rates (12.2%) as a single agent in the first-line setting. The objective of the current study was to determine whether adding the mammalian target of rapamycin inhibitor temsirolimus to sorafenib could improve on these results. METHODS: In this single-institution, phase 2 study, 36 patients with metastatic, radioactive iodine-refractory thyroid carcinoma of follicular origin received treatment with the combination of oral sorafenib (200 mg twice daily) and intravenous temsirolimus (25 mg weekly). The receipt of prior systemic treatment with cytotoxic chemotherapy and targeted therapy, including sorafenib, was permitted. The primary endpoint was the radiographic response rate. RESULTS: The best response was a partial response in 8 patients (22%), stable disease in 21 (58%), and progressive disease in 1 (3%). Six patients were not evaluable for a response. Patients who had received any prior systemic treatment had a response rate of 10% compared with 38% of those who had not received prior systemic treatment. One of 2 patients with anaplastic thyroid cancer had an objective response. The progression-free survival rate at 1 year was 30.5%. The most common grade 3 and 4 toxicities associated with sorafenib and temsirolimus included hyperglycemia, fatigue, anemia, and oral mucositis. CONCLUSIONS: Sorafenib and temsirolimus appear to be an active combination in patients with radioactive iodine-refractory thyroid carcinoma, especially in patients who received no prior treatment compared with historic data from single-agent sorafenib. Activity is also observed in patients who previously received sorafenib. This regimen warrants further investigation. Cancer 2017;123:4114–4121. © 2017 American Cancer Society. © 2017 American Cancer Society
Keywords: sorafenib; thyroid cancer; anaplastic thyroid cancer; mammalian target of rapamycin (mtor) inhibition; v-raf murine sarcoma viral oncogene homolog b (braf) mutation
Journal Title: Cancer
Volume: 123
Issue: 21
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2017-11-01
Start Page: 4114
End Page: 4121
Language: English
DOI: 10.1002/cncr.30861
PROVIDER: scopus
PMCID: PMC5650535
PUBMED: 28662274
DOI/URL:
Notes: Article -- Export Date: 1 November 2017 -- Source: Scopus
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MSK Authors
  1. James A Fagin
    111 Fagin
  2. Camelia S Sima
    204 Sima
  3. Ronald A Ghossein
    305 Ghossein
  4. Eric J Sherman
    152 Sherman
  5. Sofia S Haque
    77 Haque
  6. David G Pfister
    251 Pfister
  7. Shrujal S Baxi
    70 Baxi
  8. Matthew G Fury
    93 Fury
  9. Alan Loh Ho
    85 Ho
  10. Lara   Dunn
    26 Dunn
  11. Grace Dalton Cullen
    5 Cullen