Endocrine Abstracts

Background: Several adverse events are recorded during treatment with tyrosine-kinase inhibitors (TKIs). Hypocalcemia was reported during phase III clinical trials with both Lenvatinib and Vandetanib, but scanty data are available in a real-life setting. Aim of our study was to evaluate hypocalcemia occurrence and its characteristics in a cohort of patients treated with these drugs for advanced thyroid cancer. Moreover, in patients treated with Lenvatinib, we examined a possible correlation between hypocalcemia occurrence and TKI efficacy.

Methods: We retrospectively evaluated all patients treated with Lenvatinib and Vandetanib in our centre from June 2008 and March 2023. We included patients with a follow-up of more than 3 months and with available data about calcium levels. Lenvatinib efficacy was evaluated as progression free survival (PFS) and overall survival (OS).

Results: We included 34 patients: 28 patients treated with Lenvatinib for differentiated thyroid cancer and 6 patients treated with Vandetanib for medullary thyroid cancer. In the Lenvatinib group, after a median follow-up of 33 months (range 4-78 months), 6 patients (21.4%) recorded hypocalcemia and in two of them (7.1%) it was of grade ≥ 3. The average time of the first hypocalcemia occurrence was 3 months (range 0.5-13 months); two patients with hypocalcemia had a secondary hyperparathyroidism, while four patients had low or inappropriately normal PTH levels. No differences were found in terms of gender, age at diagnosis, presence of post-surgical hypoparathyroidism, length of treatment, dose at start and mean dose of Lenvatinib. Median PFS was 22.8 and 28.3 months and median OS was 32.2 and 33.5 months in hypocalcemic and eucalcemic groups, respectively (P = NS). Only 1/6 patients (16.7%) on Vandetanib recorded hypocalcemia, after a median follow of 88 months (range 20-176 months). Hypocalcemia occurred after 48 months of treatment. It was of grade 1 and associated to secondary hyperparathyroidism.

Conclusions: Hypocalcemia was reported in more than 20% of patients treated with Lenvatinib and it was milder and less frequent during Vandetanib treatment. During Lenvatinib, hypocalcemia was an early adverse event, usually occurring during the first 3 months of treatment. Both PTH-dependent and PTH-independent mechanisms are involved in the development of this adverse event. The occurrence of hypocalcemia was not associated to drug efficacy during Lenvatinib treatment. Since hypocalcemia can be severe, a periodic assessment of phosphocalcic metabolism is recommended to prevent the possible severe consequences of this TKI side effect.