Endocrine Abstracts

Objectives: Lenvatinib treatment significantly improves the outcome in advanced, radioiodine refractory, differentiated thyroid cancer (DTC) patients. The treatment efficacy relies on maintaining the drug dose intensity, which can be complex due to lenvatinib toxicities. Data from the SELECT study showed that interruptions for over 10% of the treatment period detrimentally affects prognosis. Nevertheless, the increasing knowledge from real-life experiences resulted in improved management of adverse events (AEs), thus reducing the need for prolonged suspensions. The impact of brief lenvatinib withdrawals remains unclear. Short, programmed drug holidays during treatment are reported to improve prognosis, but data are scarce. This study aims to assess the impact of short lenvatinib interruptions in DTC patients.

Methods: We retrospectively analysed 31 patients with advanced DTC treated with lenvatinib in our tertiary care centre. The primary outcome was the effect of short (<10% of treatment period) lenvatinib interruptions on the treatment efficacy and safety. Efficacy was evaluated as progression-free survival (PFS) and overall survival (OS). Safety was assessed as time to the first dose reduction (TFR), that is the interval between treatment initiation and the first dose reduction due to AEs. Comparison between subgroups was performed by Kaplan-Meyer survival analysis.

Results: For efficacy analysis, we compared PFS and OS of patients who transiently interrupted lenvatinib for ≤1% (n = 16) and >1% (n = 15) of the time between lenvatinib initiation and either disease progression or death. The two groups were similar according to sex, age, tumour characteristics, metastasis location, follow-up length, and lenvatinib starting dose. Median PFS did not differ between ≤1% and >1% withdrawal groups (39 vs 42 months, P = 0.78). Median OS was not reached in both groups, with no significant differences (P = 0.36). For safety evaluation, we compared TFR of patients who transiently interrupted (n = 12) and did not interrupt (n = 19) lenvatinib before dose reduction. Groups were similar for most anamnestic and clinical characteristics, including frequency of grade ≤2 (66.7 vs 73.7%) and grade >2 (26.3 vs 33.3%) toxicities (P = 0.32). Median lenvatinib starting dose was lower in patients who transiently interrupted lenvatinib before dose reduction (12 vs 20 mg, P = 0.02). Median TFR was significantly longer in this subgroup (22.4 vs 5.5 months, P = 0.049). Nevertheless, neither suspensions nor lenvatinib starting dose independently predicted prolonged TFR in Cox regression analysis.

Conclusions: Results from our study demonstrate that short lenvatinib interruptions do not impair DTC patient outcomes. Conversely, they may improve therapy compliance by delaying the need for dose reduction.