Endocrine Abstracts

Objectives: Lenvatinib treatment is responsible for several adverse events (AEs). Hypocalcemia has been described in the registration study in 7% of patients, being of grade ≥3 in 2.7% of cases. No real-life studies are available, and the actual impact of this AE during Lenvatinib treatment is still unknown. Aim of our study is to evaluate the frequency of hypocalcemia in our series of patients treated with Lenvatinib and the possible predictors of this side effect.

Methods: We included all patients who were treated with Lenvatinib for progressive radioiodine refractory thyroid cancer at our Institution. We excluded patients who had a follow-up of less than 6 months and for whom information about calcium levels was not available.

Results: We included 25 patients who received Lenvatinib treatment for a mean of 29 months (range 6-68 months). Hypocalcemia was recorded in 6/25 patients (24%) and it was of grade ≥3 in 2/25 patients (8%). Hypocalcemia occurred after a mean of 5 months (range 0.5-13 months) from the start of Lenvatinib. It was managed with calcium oral supplementation or intravenous treatment, when necessary, and Lenvatinib was transiently withdrawn in 2/6 patients. No significant differences were found among who developed and who did not develop hypocalcemia in terms of gender (females were 50% and 57.9% respectively), age at start of Lenvatinib (69.8 vs 65.9 years old), starting dose of Lenvatinib (mean dose was 17.7 mg vs 16.6 mg), length of treatment (mean duration was 23 vs 31 months), post-thyroidectomy hypoparathyroidism (16.7% vs 10.5%). All patients who had hypocalcemia and for whom a bone densitometry evaluation was available had osteoporosis (3/3), while among patients who did not experience hypocalcemia 4/6 (66.7%) had osteoporosis (P=0.28). Finally, 2 patients with normal post-surgical PTH levels, developed a grade ≥3 hypocalcemia with low (12.6 ng/l) or inappropriately normal (46.9 ng/l, n.v.13-64 ng/l) PTH levels during the hypocalcemic crisis.

Conclusions: Hypocalcemia is a frequent AE during Lenvatinib. Since it can be a life-threatening AE, monitoring of calcium levels following the start of treatment is mandatory and we recommend a particular caution during the first year of treatment. Oral calcium supplementation can correct hypocalcemia if promptly diagnosed; however, up to 10% of patients may have a severe hypocalcemia requiring intravenous treatment and Lenvatinib transient interruption. Further studies are needed to get more insights into the pathogenesis of hypocalcemia during Lenvatinib, though an inappropriate response of PTH to hypocalcemia has been observed.