Continuous administration of lenvatinib after first documented disease progression in patients with radioiodine-refractory thyroid cancer.

purposeTo determine the efficacy and safety of lenvatinib beyond first documented disease progression (LBP) and prognostic factors after progression in patients with radioiodine-refractory thyroid cancer.

methodsThis retrospective study included adults with radioiodine-refractory thyroid cancer who received lenvatinib between January 2012 and November 2023 and continued treatment after initial RECIST 1.1 progression. Patients who subsequently received other multikinase inhibitors or selective targeted therapies were excluded. Time to second treatment failure (second TTF) was defined as time from initial progression to permanent lenvatinib discontinuation for any reason; second progression-free survival (second PFS) as time from initial progression to subsequent radiographic progression or death; and post-progression survival (PPS) as time from initial progression to death. Outcomes were estimated by Kaplan–Meier methods, and prognostic factors were explored by Cox regression. Safety was assessed.

resultsTwenty-four patients met the eligibility criteria for LBP. The objective response rate after progression was 0%, whereas the disease control rate was 50.0%. Median second PFS and second TTF were 6.0 months and 8.0 months, respectively. Median PPS was 14.8 months. At 12 months after initial progression, 37.5% of patients remained on lenvatinib and 56.5% were alive. Baseline progressive disease at initial progression (tumor burden returning to or exceeding the pretreatment baseline) was associated with shorter second TTF, with similar trends for second PFS and PPS. The most common adverse events were hypertension, proteinuria, peripheral edema, and renal dysfunction.

conclusionContinuation of lenvatinib beyond disease progression achieved modest additional disease control with acceptable safety in selected patients. In settings where access to subsequent-line systemic therapies is limited or no actionable targets are identified, LBP may serve as a pragmatic bridging approach for carefully selected patients.