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The Efficacy and Safety of Surufatinib Combined with Anti PD-1 Antibody Toripalimab in Neoadjuvant Treatment of Locally Advanced Differentiated Thyroid Cancer: A Phase II Study

  • Endocrine Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Surgery is the primary treatment for locally advanced differentiated thyroid cancer (DTC). However, some locally advanced patients are not candidates for R0/1 resection. There is limited evidence of neoadjuvant treatment in locally advanced DTC. Surufatinib targets multiple kinases, which is efficient, tolerable, and safe in patients with radioiodine-refractory DTC. In addition, surufatinib plus toripalimab (an anti-PD-1 antibody) showed encouraging antitumor activity in advanced solid tumors. This study was designed to evaluate the efficacy and safety of surufatinib plus toripalimab in locally advanced DTC in the neoadjuvant setting.

Methods

In this single-arm, phase II study, patients with pathologically confirmed unresectable or borderline resectable DTC were eligible and received a combination of 250 mg of surufatinib (orally daily) with 240 mg of toripalimab (intravenous, every 3 weeks). Treatment continued until satisfied for curative surgery, disease progression, withdrawal of consent, unacceptable toxicity, or investigator decision. Primary endpoint was objective response rate (ORR). Secondary endpoints included R0/1 resection rate, adverse events (AEs), etc.

Results

Ten patients were enrolled and received at least 4 cycles of treatment. The ORR was 60%. Nine patients received R0/1 resections after neoadjuvant treatment. The median best percentage change in the sum of the target lesion diameter was 32%. Most adverse events (AEs) were grade 1 or 2.

Conclusions

Surufatinib in combination with toripalimab as neoadjuvant therapy for locally advanced DTC was feasible, and the majority of patients achieved R0/1 resection. It represents a new option for locally advanced DTC and needs further investigation.

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References

  1. Yang L, Shen W, Sakamoto N. Population-based study evaluating and predicting the probability of death resulting from thyroid cancer and other causes among patients with thyroid cancer. J Clin Oncol. 2013;31:468–74.

    Article  PubMed  Google Scholar 

  2. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.

    Article  PubMed  Google Scholar 

  3. Wang LY, Nixon IJ, Patel SG, et al. Operative management of locally advanced, differentiated thyroid cancer. Surgery. 2016;160:738–46.

    Article  PubMed  Google Scholar 

  4. Hartl DM, Zago S, Leboulleux S, et al. Resection margins and prognosis in locally invasive thyroid cancer: Invasive thyroid cancer. Head Neck. 2014;36:1034–8.

    Article  PubMed  Google Scholar 

  5. Gaissert HA, Honings J, Grillo HC, et al. Segmental laryngotracheal and tracheal resection for invasive thyroid carcinoma. Ann Thorac Surg. 2007;83:1952–9.

    Article  PubMed  Google Scholar 

  6. Lim H, Devesa SS, Sosa JA, Check D, Kitahara CM. Trends in thyroid cancer incidence and mortality in the United States, 1974–2013. JAMA. 2017;317:1338.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kitamura Y, Shimizu K, Nagahama M, et al. Immediate causes of death in thyroid carcinoma: Clinicopathological analysis of 161 fatal cases. J Clin Endocrinol Metab. 1999;84:4043–9.

    Article  CAS  PubMed  Google Scholar 

  8. Aw TC, Seah HC, Cheah JS. Medullary carcinama of the thyroid presenting as final asphyxia. Med J Aust. 1979;1:188–91.

    Article  CAS  PubMed  Google Scholar 

  9. Beasley NJP, Walfish PG, Witterick I, Freeman JL. Cause of death in patients with well-differentiated thyroid carcinoma. Laryngoscope. 2001;111:989–91.

    Article  CAS  PubMed  Google Scholar 

  10. Ishihara T, Yamazaki S, Kobayashi K, et al. Resection of the trachea infiltrated by thyroid carcinoma. Ann Surg. 1982;195:496–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Li Y, Wang J, Ma X, et al. A review of neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Int J Biol Sci. 2016;12:1022–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kasi A, Abbasi S, Handa S, et al. Total neoadjuvant therapy vs standard therapy in locally advanced rectal cancer: a systematic review and meta-analysis. JAMA Netw Open. 2020;3:e2030097.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Petrelli F, Trevisan F, Cabiddu M, et al. Total neoadjuvant therapy in rectal cancer: a systematic review and meta-analysis of treatment outcomes. Ann Surg. 2020;271:440–8.

    Article  PubMed  Google Scholar 

  14. Patel S, Kapoor A. Intensifying neoadjuvant treatment in locally advanced rectal cancer. Lancet Oncol. 2021;22:e301.

    Article  PubMed  Google Scholar 

  15. Cleary JM, Sadow PM, Randolph GW, et al. Neoadjuvant treatment of unresectable medullary thyroid cancer with sunitinib. J Clin Oncol. 2010;28:e390–2.

    Article  PubMed  Google Scholar 

  16. Tsuboi M, Takizawa H, Aoyama M, Tangoku A. Surgical treatment of locally advanced papillary thyroid carcinoma after response to lenvatinib: a case report. Int J Surg Case Rep. 2017;41:89–92.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Danilovic DLS, Castro G, Roitberg FSR, et al. Potential role of sorafenib as neoadjuvant therapy in unresectable papillary thyroid cancer. Arch Endocrinol Metab. 2018;62:370–5.

    PubMed  PubMed Central  Google Scholar 

  18. Jozaghi Y, Zafereo M, Williams MD, et al. Neoadjuvant selpercatinib for advanced medullary thyroid cancer. Head Neck. 2021;43:E7-12.

    Article  PubMed  Google Scholar 

  19. Huang N, Wei W, Xiang J, et al. The efficacy and safety of anlotinib in neoadjuvant treatment of locally advanced thyroid cancer: a single-arm phase II clinical trial. Thyroid. 2021;31:1808–13.

    Article  CAS  PubMed  Google Scholar 

  20. Koumarianou A, Kaltsas G. Surufatinib: a novel oral agent for neuroendocrine tumours. Nat Rev Endocrinol. 2021;17:9–10.

    Article  CAS  PubMed  Google Scholar 

  21. Chen J, Ji Q, Bai C, et al. Surufatinib in chinese patients with locally advanced or metastatic differentiated thyroid cancer and medullary thyroid cancer: a multicenter, open-label, phase II trial. Thyroid. 2020;30:1245–53.

    Article  CAS  PubMed  Google Scholar 

  22. Keam SJ. Toripalimab: first global approval. Drugs. 2019;79:573–8.

    Article  CAS  PubMed  Google Scholar 

  23. Mehnert JM, Varga A, Brose MS, et al. Safety and antitumor activity of the anti–PD-1 antibody pembrolizumab in patients with advanced, PD-L1–positive papillary or follicular thyroid cancer. BMC Cancer. 2019;19:196.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Gunda V, Gigliotti B, Ashry T, et al. Anti-PD-1/PD-L1 therapy augments lenvatinib’s efficacy by favorably altering the immune microenvironment of murine anaplastic thyroid cancer: combining lenvatinib and anti-PD-1/PD-L1 therapy in orthotopic murine anaplastic thyroid cancer. Int J Cancer. 2019;144:2266–78.

    Article  CAS  PubMed  Google Scholar 

  25. Li J, Zhang X, Mu Z, Sun D, Sun Y, Lin Y. Response to apatinib and camrelizumab combined treatment in a radioiodine refractory differentiated thyroid cancer patient resistant to prior anti-angiogenic therapy: a case report and literature review. Front Immunol. 2022;13:943916.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lee MS, Ryoo B-Y, Hsu C-H, et al. Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): an open-label, multicentre, phase 1b study. Lancet Oncol. 2020;21:808–20.

    Article  CAS  PubMed  Google Scholar 

  27. Zhou J, Ni J, Cheng M, et al. Preclinical evaluation of sulfatinib, a novel angio-immuno kinase inhibitor targeting VEGFR, FGFR-1 and CSF-1R kinases. AACR Abstract. 2017;77:4187.

    Google Scholar 

  28. Cao Y, Lu M, Sun Y, et al. Surufatinib plus toripalimab in patients with advanced solid tumors: a single-arm, open-label, phase 1 trial. J Cancer Res Clin Oncol. 2022;149:779–89.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Iwasaki H, Toda S, Ito H, et al. A case of unresectable papillary thyroid carcinoma treated with lenvatinib as neoadjuvant chemotherapy. Case Rep Endocrinol. 2020;2020:1–4.

    Article  Google Scholar 

  30. Stewart KE, Strachan MWJ, Srinivasan D, MacNeill M, Wall L, Nixon IJ. Tyrosine kinase inhibitor therapy in locally advanced differentiated thyroid cancer: a case report. Eur Thyroid J. 2019;8:102–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Nava CF, Scheffel RS, Cristo AP, et al. Neoadjuvant multikinase inhibitor in patients with locally advanced unresectable thyroid carcinoma. Front Endocrinol. 2019;10:712.

    Article  Google Scholar 

  32. Drilon A, Oxnard GR, Tan DSW, et al. Efficacy of selpercatinib in RET fusion–positive non–small-cell lung cancer. N Engl J Med. 2020;383:813–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Subbiah V, Cassier PA, Siena S, et al. Pan-cancer efficacy of pralsetinib in patients with RET fusion–positive solid tumors from the phase 1/2 ARROW trial. Nat Med. 2022;28:1640–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Cabanillas ME, Ferrarotto R, Garden AS, et al. Neoadjuvant BRAF- and Immune-Directed therapy for anaplastic thyroid carcinoma. Thyroid. 2018;28:945–51.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Dierks C, Seufert J, Aumann K, et al. Combination of lenvatinib and pembrolizumab is an effective treatment option for anaplastic and poorly differentiated thyroid carcinoma. Thyroid. 2021;31:1076–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zhang G, Wei W, Song H, et al. Programmed cell death–Ligand overexpression in thyroid cancer. Endocr Pract. 2019;25:279–86.

    Article  PubMed  Google Scholar 

  37. Bastman JJ, Serracino HS, Zhu Y, et al. Tumor-Infiltrating T cells and the PD-1 checkpoint pathway in advanced differentiated and anaplastic thyroid cancer. J Clin Endocrinol Metab. 2016;101:2863–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Adam P, Kircher S, Sbiera I, et al. FGF-receptors and PD-L1 in anaplastic and poorly differentiated thyroid cancer: evaluation of the preclinical rationale. Front Endocrinol. 2021;12:712107.

    Article  Google Scholar 

  39. Voron T, Colussi O, Marcheteau E, et al. VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J Exp Med. 2015;212:139–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Katoh M. FGFR inhibitors: effects on cancer cells, tumor microenvironment and whole-body homeostasis (Review). Int J Mol Med. 2016;38:3–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgment

The results of this trial (abstract 6084) were presented on the 2022 American Society of Clinical Oncology (ASCO) annual meeting.

Funding

This work was supported by Shanghai Shenkang Hospital Development Centre (SHDC22021201).

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Authors and Affiliations

  1. Department of Head and Neck Surgery, Fudan University Shanghai Cancer Centre, Shanghai, China

    Jia-ying Chen MD, PhD, Nai-si Huang MD, PhD, Wen-jun Wei MD, PhD, Jia-qian Hu MD, PhD, Yi-ming Cao MD, Qiang Shen MD, Zhong-wu Lu MD, Yu-long Wang MD, PhD, Yu Wang MD, PhD & Qing-hai Ji MD, PhD

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Jia-ying Chen MD, PhD, Nai-si Huang MD, PhD, Wen-jun Wei MD, PhD, Jia-qian Hu MD, PhD, Yi-ming Cao MD, Qiang Shen MD, Zhong-wu Lu MD, Yu-long Wang MD, PhD, Yu Wang MD, PhD & Qing-hai Ji MD, PhD

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  1. Jia-ying Chen MD, PhD
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Correspondence to Yu-long Wang MD, PhD, Yu Wang MD, PhD or Qing-hai Ji MD, PhD.

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Chen, Jy., Huang, Ns., Wei, Wj. et al. The Efficacy and Safety of Surufatinib Combined with Anti PD-1 Antibody Toripalimab in Neoadjuvant Treatment of Locally Advanced Differentiated Thyroid Cancer: A Phase II Study. Ann Surg Oncol 30, 7172–7180 (2023). https://doi.org/10.1245/s10434-023-14031-z

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  • DOI: https://doi.org/10.1245/s10434-023-14031-z

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