A new therapeutic paradigm: radioiodine combined with lenvatinib for radioiodine-avid metastatic well-differentiated thyroid cancer.

Abstract

Purpose: Management of metastatic well-differentiated thyroid cancer (WDTC) remains challenging, with significant morbidity and mortality. Multidisciplinary treatment, along with high-dose radioiodine therapy (HDRI), remains a mainstay. Morbidity and mortality benefits are noted, with seldom complete response. The foremost concerns are HDRI side effects, radioiodine refractoriness, macronodular lung, and bone metastasis. Lenvatinib is a standard of care in radioiodine-refractory disease. However, it remains unexplored in radioiodine-avid metastatic WDTC. This study investigates the effect of lenvatinib with HDRI in improving disease control and progression in radioiodine-avid metastatic WDTC.

Material and methods: Fifteen patients with metastatic WDTC were enrolled with or without prior HDRI. The disease burden was evaluated with imaging [whole-body radioiodine scan (WBRI), PET-computed tomography (CT), or CT] and serum thyroglobulin (Tg) measurement. After excluding contraindication, lenvatinib was given for 3 months, along with thyroxine suppression. Adverse effects were monitored. Thyroxin was withdrawn, and the patient underwent WBRI followed by HDRI. Treatment response was evaluated based on imaging [response evaluation criteria in solid tumors (RECIST), PET response criteria in solid tumors (PERCIST), and WBRI] and tumor marker (Tg) parameters.

Results: The mean age was 52.0 ± 14.2 years. Lung and bone metastases were noted in (12, 80%) and 10 (66%) patients. Nine (60%) patients already had HDRI (242.5 ± 140.3 mCi). Lenvatinib was well-tolerated, with two-thirds of patients having grade I toxicities. During follow-up (14.79 ± 5.93 months), one patient died of pneumonia unrelated to WDTC. Tg level fell from 45 800.8 ± 69 283.9 [median: 7094.0, interquartile range (IQR): 988.3-114 397.0] to 10 672.5 ± 18 490.5 (median: 1796.0, IQR: 171.0-17 090.0) ng/ml. Tg fall was not associated (P > 0.05) with age, sex, histopathology, and previous HDRI. Partial response and stable disease were noted in 10 and four patients, respectively, based on imaging (PERSIST and RECIST criteria) and tumor marker levels. One patient had disease progression on Tg and imaging.

Conclusion: HDRI, in combination with lenvatinib, demonstrated potential benefits in radioiodine-avid metastatic WDTC. The combination treatment was well-tolerated. There was an unprecedented fall in tumor marker level and partial response on imaging by a single cycle of the therapy. While a small sample size limited the study, preliminary data suggest that the synergistic effect may improve disease control. Further investigation with a larger cohort is warranted to confirm findings and explore potential response predictors.