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Outcome of Patients with Locally Advanced Metastatic Medullary Thyroid Cancer and Induction Therapy with Tyrosine Kinase Inhibitors in Slovenia

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Abstract

Background

The aim of our retrospective study was to evaluate the outcome of patients with metastatic medullary thyroid cancer (MTC) treated with tyrosine kinase inhibitors (TKIs) and/or chemotherapy with the emphasis on analysis on the cohort treated by induction TKI because of locally advanced metastatic MTC.

Methods

We analyzed the outcome of 30 patients (21 males, 9 females; median age 63.8 years) with metastatic MTC treated between 2000–2020. Sunitinib was used in 20 patients.

Results

Median progression-free survival on TKI and on chemotherapy was 10.6 (95% CI 7.1–14) months and 3.5 (95% CI 1.4–5.5) months, respectively. Median overall survival from diagnosis and from metastasis presentation was 38.2 (95% CI 4.7–71.7) months and 20.9 (95% CI 13.8–27.9) months, respectively. Eight patients (five females, three males; 58–86 years of age, median age 70 years) were treated with induction TKI because of inoperable locally advanced and metastatic MTC. The response rate to induction TKI was 50%; two patients (25%) had stable disease, and two patients (25%) had progressive disease.

Conclusion

Our data support a new paradigm that TKIs may be the first treatment option in selected patients with locally advanced metastatic MTC, followed by locoregional treatment with surgery and/or external beam radiotherapy. Further studies are required to consolidate the presented data.

Plain Language Summary

A new paradigm of surgery after neoadjuvant/induction tyrosine kinase inhibitors is not accepted as a standard of care in patients with medullary thyroid cancer. The aim of our retrospective study was to evaluate the outcome of all patients with metastatic medullary cancer treated in a 20-year period in Slovenia and, among these, the cohort treated with induction tyrosine kinase inhibitors because of locally advanced metastatic medullary thyroid cancer. Our first hypothesis was that the outcome of metastatic medullary cancer treated with tyrosine kinase inhibitors is better than in those treated with chemotherapy. Our second hypothesis was that induction therapy with tyrosine kinase inhibitors was effective in the treatment of initially inoperable primary tumors. In the treatment of metastatic medullary cancer a systemic therapy was used in 83.4% (25/30) patients. Patients on targeted treatment with tyrosine kinase inhibitors had more often a partial remission than on chemotherapy (65% vs. 17%, respectively). Eight patients were treated with induction tyrosine kinase inhibitors because of locally advanced metastatic disease. The computer tomography evaluation of the primary tumor during tyrosine kinase inhibitor therapy revealed partial response in four cases and stable disease in four cases, but surgery was performed in two cases only. Our data support a new paradigm that tyrosine kinase inhibitors may be the first treatment option in patients with locally advanced metastatic medullary thyroid carcinoma followed by locoregional treatment with surgery and/or external beam radiotherapy. However, further studies are required to consolidate the presented data.

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Acknowledgements

We thank the participants of the study.

Funding

This research and Rapid Service Fee were funded by the Ministry of Education, Science and Sport of the Republic of Slovenia, grant P3-0289, Ljubljana, Slovenia.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Author Contributions

Conceptualization, CGK and NB; methodology, CGK; formal analysis, CGK; investigation, MMM; data curation, TL and MMM; writing—original draft preparation, CGK; writing—review and editing, NB and CGK; visualization, CGK; supervision, CGK; funding acquisition, NB. All authors have read and agreed to the published version of the manuscript. Correspondence and requests for materials should be addressed to NB.

Disclosures

Cvetka Grasic Kuhar has provided consulting services for Bayer on unrelated projects. Taja Lozar, Nikola Besic, and Maja Music Marolt have nothing to disclose.

Ethics Approval

The study was reviewed and approved by the Protocol Review Board (ERID-KSOPKR-0082/2020) and the Ethics Committee of the Institute of Oncology Ljubljana (ERIDEK-0083/2020) and was conducted in accordance with the Declaration of Helsinki of 1964 and its later amendments. Patient consent was waived by the Ethics Committee of the Institute of Oncology Ljubljana (ERIDEK-00575/2018; 15 March 2018) because of the retrospective nature of our study.

Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Medical Oncology, Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia

    Cvetka Grasic Kuhar & Taja Lozar

  2. Faculty of Medicine Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia

    Cvetka Grasic Kuhar, Taja Lozar, Nikola Besic & Maja Music Marolt

  3. Department of Surgical Oncology, Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia

    Nikola Besic

  4. Department of Radiology, Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia

    Maja Music Marolt

Authors
  1. Cvetka Grasic Kuhar
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Corresponding author

Correspondence to Nikola Besic.

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Grasic Kuhar, C., Lozar, T., Besic, N. et al. Outcome of Patients with Locally Advanced Metastatic Medullary Thyroid Cancer and Induction Therapy with Tyrosine Kinase Inhibitors in Slovenia. Adv Ther 38, 5684–5699 (2021). https://doi.org/10.1007/s12325-021-01940-2

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  • DOI: https://doi.org/10.1007/s12325-021-01940-2

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