Low Dose of Lenvatinib Treatment for Patients of Radioiodine-Refractory Differentiated Thyroid Carcinoma – A Real-World Experience

Abstract

Background

Lenvatinib treatment of 24 mg/day for radioiodine-refractory differentiated thyroid carcinoma (RRDTC) patients was almost intolerable, with high rates of dose reduction, interruption and discontinuation. Balancing treatment safety with disease risks remains challenging, and the appropriate dosage remains unclear in Asia.

Patients and Methods

A total of 65 RRDTC patients treated with lenvatinib were retrospectively collected from Oct. 2015 to Jun. 2020 from two medical centers of South Taiwan. The drug tolerability, treatment efficacy and clinical outcomes were analyzed.

Results

Different doses of lenvatinib were initiated but ultimately maintained with a median dose of 10 mg/day within the first 3 months. The disease control rate reached 89.2%, including 24.6% partial response and 64.6% stable disease. Disease progression occurred in 10.8% of patients and increased to 40.0% at the end. Eventually, the treatment dose achieved a median progression-free survival (PFS) of 26.1 months (95% CI: 17.1-NA) with overall survival (OS) not reached yet (24.1~NA). Overall, the 48-month PFS rate was 35.6% (95% CI: 18.5–68.4) and 48-month OS was 54.3% (95% CI: 41.2–71.7). The dose was tolerable with a dose reduction rate of 44.6%, dose interruption rate of 40.0% and fewer high-graded adverse events. The drug discontinuation rate was only 3.1%. However, RRDTC patients with bone metastasis or maximal dose exposure to RAI (≥600 mCi) may have less efficacy to the low maintenance dose treatment.

Conclusion

Assessing treatment intensity, safety and efficacy, low-dose lenvatinib treatment was well tolerated by RRDTC patients and displayed acceptable drug efficacy and outcomes.

Keywords:

• lenvatinib
• radioiodine-refractory differentiated thyroid carcinoma
• RRDTC
• disease control rate
• DCR
• progression-free survival
• PFS
• overall survival
• OS

Acknowledgments

The authors are grateful to Sin-Hua Moi, PhD, Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan, for her valuable assistance with statistical analysis.

Abbreviations

RRDTC, radioiodine-refractory differentiated thyroid carcinoma; PFS, progression-free survival; OS, overall survival; DCR, Disease control rate; PFS, Progression-free survival; OS, Overall survival; DTC, differentiated thyroid carcinoma; RAI, radioiodine; TKI, multi-kinase inhibitor; AEs, adverse events; DCR, disease control rate; ECOG, Eastern Cooperative Oncology Group; RECIST, Response Evaluation Criteria in Solid Tumors; CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; IOR, interquartile range; CIs, confidence intervals; PR, partial response; SD, stable disease; PD, progressive disease; NA, not available; QoL, quality of residual life; DOR, duration of response.

Ethics Approval and Informed Consent

This case series study was conducted and approved by the Institutional Review Boards of Medical centers of Kaohsiung Medical University (KMUHIRB-E (I)-20190014) and Kaohsiung Chang-Gung Memorial Hospital (CGMHIRB No. 201801270B0).

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

All authors declared that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.