Real-life Tolerance and Plasma Exposure Assessment of Lenvatinib in Thyroid Metastatic Cancer Patients

Background: Lenvatinib (LenvimaTM, LVT), an oral tyrosine kinase inhibitor, has shown efficacy in iodine-131–refractory thyroid cancer with a median progression free survival (PFS) in the LVT 24 mg daily arm of 18.3 months compared to 3.6 months in the placebo arm. Yet, with a 97.3% incidence of all grades treatment-related adverse effects, dose interruption or dose reduction occur at 82.4% and 67.8%, respectively. The objective of this study was to assess real-life tolerance and LVT plasma exposure after dose reduction in thyroid cancer patients. Methods: This monocentric prospective observational study included metastatic differentiated thyroid cancer patients treated with LVT in monotherapy according a signed informed consent. Toxicity evaluation was performed monthly after lenvatinib initiation according CTCAE guidelines. Biological parameters, concomitant treatment, morphological tumoral response were also recorded. Blood samples were collected monthly. LVT plasma concentrations were quantified using a routine LC-MS/MS method. A previously published population pharmacokinetic model of LVT was used to compute the individual PK parameters AUC0-24h and Ctrough with NONMEM software (version 7.2). PK parameters in patients experiencing or not adverse event were compared using Wilcoxon test. Results: LVT Dose reduction occurred in the 13 included patients during the month following LVT initiation (20mg QD n = 1; 14mg QD n = 6; 10mg QD n = 6). Over the 45 observations, median AUC0-24h reached 1797.2 [984.9 to 3169.8] ng.h.mL−1. LVT treatment was generally well-tolerated as grade 3 HTA events were reported in only 4 patients and did not lead to treatment discontinuation. To date, treatment duration ranged from 3 to 15 months. Grade 1 and 2 diarrhea, hypertension, asthenia occurred during the follow-up, but only HTA appears to be associated with plasma concentration (p = 0.79, p = 0.033 and p = 0.39 respectively). Conclusions: LVT was well tolerated and no treatment discontinuation was needed. Despite systematic dose reduction, plasma exposure was consistent with the expected exposure at the initial dose. Further exploration is needed to assess treatment duration and tumoral response in real-life treated patients. Legal entity responsible for the study: Assistance Publique des Hôpitaux de Paris Funding: Has not received any funding Disclosure: C. Chougnet: Has a conflict of interest with EISAI. All other authors have declared no conflicts of interest.