Radioiodine Plus Low-Dose Lenvatinib in Radioiodine-Sensitive High-Volume Metastatic Differentiated Thyroid Cancer: A Pilot Study.

Abstract

Radioactive iodine (RAI) therapy is the standard-of-care for metastatic differentiated thyroid cancer (DTC), but ~60% of patients show resistance before achieving satisfactory response. Eligible patients were randomly assigned to RAI therapy plus lenvatinib (RAI-L arm) or standard RAI therapy alone (RAI arm). All patients were administered RAI therapy (5.5-7.4 GBq) every 6-9 months, and patients in RAI-L arm were additionally administered lenvatinib (10 mg once daily). The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival, quality of life, and toxicity. Fifty patients were enrolled (mean age 49.1±12.6 y, range 21-67). ORR was significantly higher in the RAI-L arm compared with RAI arm (54.5% vs. 24%; P =0.03). Subgroup analysis indicated combination therapy was more beneficial in age older than or equal to 55 years ( P =0.04), follicular thyroid carcinoma ( P =0.04), presence of both pulmonary and extra-pulmonary metastases ( P =0.007), and RAI therapy-naive ( P =0.02) patients. Median PFS in the RAI-L arm was 36 months (95% CI: 24.5-47.5) versus 26 months (95% CI: 18.9-33.1) in the RAI arm ( P =0.09). Grade ≥3 adverse events were more frequent in the RAI-L arm (45.5%) compared with RAI arm (8%, P =0.006), with hypertension (31.8%) and hand-foot skin reaction (13.6%) being the most common. Combining RAI therapy with lenvatinib improved ORR with clinically meaningful prolongation of PFS; however, it comes with a burden of treatment-related toxicity, underscoring the need for careful patient selection.