Planned drug holidays during treatment with lenvatinib for radioiodine-refractory differentiated thyroid cancer: a retrospective study

Frontiers in Oncology

Oncology

Takao Fujisawa¹  Susumu Okano¹  Tomohiro Enokida¹  Makoto Tahara¹  Kazue Ito²  Yuri Ueda³  Shinya Suzuki⁴  Chihiro Matsuyama⁵ 

[1] Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan;Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan;Department of Head and Neck Medical Oncology, Miyagi Cancer Center, Natori, Japan;Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan;Department of Otorhinolaryngology-Head and Neck Surgery, Tokyo Medical University, Shinjuku, Japan;Department of Pharmacy, National Cancer Center Hospital East, Kashiwa, Japan;Department of Pharmacy, National Cancer Center Hospital East, Kashiwa, Japan;Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan;

关键词: lenvatinib;    thyroid cancer;    oral anticancer agent;    VEGF tyrosine kinase inhibitor;    adverse events;    planned drug holidays;   

DOI  :  10.3389/fonc.2023.1139659

 received in 2023-01-07, accepted in 2023-09-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundIn the phase 3 SELECT study, lenvatinib significantly improved prognostic outcomes vs. placebo in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). However, toxicity of lenvatinib is sometimes considerable and requires frequent dose interruptions and modifications. Recently, planned drug holidays have been proposed as a means of avoiding severe adverse events (AEs).MethodsWe retrospectively reviewed medical records to compare the efficacy and safety of lenvatinib in RR-DTC patients who underwent planned drug holidays (planned holiday group) vs. those who received conventional daily oral administration (daily group).ResultsThe subjects were 25 patients in the planned holiday group and 21 in the daily group. Median age was 73 years (range 43-84) and 62 years (range 42-75), and histologic subtype of papillary/follicular was 21/4 cases and 15/6 cases, respectively. Time to treatment failure (TTF) and overall survival (OS) were significantly longer in the planned holiday group than the daily group (not reached [NR] vs. 14.9 months, hazard ratio [HR] 0.25, 95% confidence interval [Cl] 0.11-0.58, p<0.001; NR vs. 26.6 months, HR 0.20, 95% CI 0.073-0.58, p=0.001, respectively). Median progression-free survival (PFS) was NR in the planned holiday group vs. 15.1 months in the daily group (HR 0.31, 95% CI 0.14-0.68, p=0.002). Duration of the period with lenvatinib dose ≥10 mg was significantly longer in the planned holiday group (NR vs. 6.5 months, HR 0.22, 95% CI 0.10-0.49, p<0.001), and the frequency of drug interruption due to intolerable AEs was lower (68.0% vs. 95.2%, p=0.027).ConclusionPlanned drug holidays for lenvatinib demonstrated significantly longer PFS, TTF, and OS than daily oral administration, and less intolerable toxicity leading to further unplanned treatment interruption. These benefits were apparently associated with a more extended period of lenvatinib administration at ≥10 mg. These findings might contribute to a favorable patient prognosis and safer toxicity profile.

【 授权许可】

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Copyright © 2023 Matsuyama, Enokida, Ueda, Suzuki, Fujisawa, Ito, Okano and Tahara