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Utility and optimal management of planned drug holidays during lenvatinib treatment in patients with unresectable differentiated thyroid cancer: a real-world multi-center study

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Abstract

Purpose

Lenvatinib achieves favorable therapeutic outcomes for patients with radioactive iodine therapy refractory differentiated thyroid cancer (DTC); however, its use is associated with a high incidence of adverse events. To avoid severe adverse events, planned drug holidays (PDH) have been proposed. This study aimed to evaluate treatment effects, identify prognostic factors, and investigate the usefulness of PDH in patients with unresectable DTC who received lenvatinib across the multi-institutions.

Methods

Fifty-one patients with unresectable DTC treated with lenvatinib were evaluated retrospectively. Overall survival (OS) and progression-free survival (PFS) were calculated, and prognostic factors were assessed. OS, PFS, and time to treatment failure (TTF) were compared between patients with and without PDH. Lenvatinib administration schedule was evaluated in PDH.

Results

The 3-year OS and PFS rate were 53.5% and 42.1%, respectively. Multivariate analysis revealed that presence of maximum size of lung metastasis ≥10 mm was independent prognostic factor for poorer OS and PFS, and histology other than papillary thyroid carcinoma was the independent prognostic factor for poorer PFS. Twenty-five patients (49%) treated with PDH. There were significant differences in OS, PFS, and TTF between patients with and without PDH. Various schedules were used in PDH. Eight (32%) patients required switch to the different administration schedule.

Conclusion

Our results suggest that PDHs may extend OS, PFS, and TTF. In patients with PDH, various schedules used for lenvatinib administration highlight the difficulty in determining a uniform administration schedule. Therefore, it is crucial to consider the optimal lenvatinib administration schedule on a case-by-case basis.

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Acknowledgements

We thank all the patients who participate in our study, and Editage (www.editage.jp) for English language editing.

Author contributions

T.M.: Conceptualization; data curation; formal analysis; investigation; methodology; project administration; resources; visualization; writing-original draft; writing-review and editing. M.S.: Conceptualization; resources; writing-review and editing. T.K.: Conceptualization; resources; writing-review and editing. R.N.: Conceptualization; resources; writing-review and editing. T.K.: Conceptualization; resources; writing-review and editing. Y.S.: Conceptualization; resources; writing-review and editing. F.I.: Conceptualization; resources; writing-review and editing. N.N.: Conceptualization; resources; writing-review and editing. S.S.: Conceptualization; resources; writing-review and editing. H.O.: Conceptualization, methodology, project administration, resources, supervision, writing-original draft, writing-review and editing.

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Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, Tokyo, Japan

    Takuya Mikoshiba, Mariko Sekimizu, Takeyuki Kono, Ryoto Nagai & Hiroyuki Ozawa

  2. Department of Otolaryngology, Head and Neck Surgery, Japanese Red Cross Shizuoka Hospital, Shizuoka, Japan

    Taiji Kawasaki

  3. Department of Otolaryngology, Saiseikai Utsunomiya Hospital, Tochigi, Japan

    Yoichiro Sato

  4. Department of Otolaryngology, National Tokyo Medical Center, Tokyo, Japan

    Fumihiro Ito

  5. Department of Otolaryngology, Saitama City Hospital, Saitama, Japan

    Nana Nakahara

  6. Department of Otolaryngology, Head and Neck Surgery, Kawasaki Municipal Kawasaki Hospital, Kanagawa, Japan

    Seiji Shigetomi

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  1. Takuya Mikoshiba
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  2. Mariko Sekimizu
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  10. Hiroyuki Ozawa
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Correspondence to Takuya Mikoshiba.

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Mikoshiba, T., Sekimizu, M., Kono, T. et al. Utility and optimal management of planned drug holidays during lenvatinib treatment in patients with unresectable differentiated thyroid cancer: a real-world multi-center study. Endocrine (2024). https://doi.org/10.1007/s12020-024-03744-0

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