Factors involved in early lenvatinib dose reduction: a retrospective analysis

Abstract

Lenvatinib, a multi-tyrosine kinase inhibitor, has been proven to be an effective treatment option for patients with iodine-131-refractory thyroid cancer. Many adverse effects of lenvatinib have been reported; thus, dose reduction is common. However, a few studies have analyzed the causes of lenvatinib dose reduction in daily clinical practice. Here, we investigate the factors involved in early lenvatinib dose reduction to analyze lenvatinib dose modification. We analyzed 20 thyroid cancer patients who began receiving lenvatinib at the Kumamoto University Hospital Cancer Center from July 2015 to November 2016. Patients were classified into the following groups based on the time until first withdrawal or dose reduction in lenvatinib: group A (early, ≤ 10 days) and group B (other, > 10 days). Patients' clinical features and reasons for withdrawal or dose reduction were analyzed. The age range of patients was 54-91 years, and the median observation period was 293 days. There were no significant differences in the administered line of lenvatinib; the presence/absence of primary residual tumors; or the history of hypertension, proteinuria, and diarrhea between the two groups (A, n = 7; B, n = 13). The cause for initial withdrawal or dose reduction was grade 3 hypertension in all group A patients, which was significantly higher than that in group B (p = 0.0001). Our results suggest that early blood pressure control may be effective as a method to maintain the lenvatinib dose intensity.

Evaluation of the Qtc Interval During Lenvatinib Treatment in Radioiodine-Refractory Differentiated Thyroid Cancer: Reports from the Real-Life Clinical Practice

“…No QTc prolongation has been listed among the adverse events in a Phase II trial of lenvatinib in RR-DTC [10]. Similarly, other studies do not report QTc prolongation among the most frequent side effects during lenvatinib treatment [11][12][13][14] and considering cardiovascular adverse events, grade 3 (according to the adverse events scale) hypertension has been shown to represent the principal reason for early lenvatinib dose reduction in a retrospective study [15]. In the Phase III SELECT study on lenvatinib treatment in RR-DTC, QTc prolongation was found to occur in 8 and 1.5% of patients when any grade or a grade ≥3 were considered, respectively [4].…”

Survival With Lenvatinib for the Treatment of Progressive Anaplastic Thyroid Cancer: A Single-Center, Retrospective Analysis

“…Our data suggest that the addition of lenvatinib to existing anticancer drugs may increase the sensitivity to treatment; this confirms previous non-clinical research which suggested synergistic antineoplastic activity resulting from the combined use of chemotherapy, radiotherapy, and TKI inhibitors ( 23 ). However, the potential for toxicity may also increase when combining several treatment modalities; furthermore, AEs are commonly reported with TKI treatment ( 24 , 25 ). Nonetheless, these may be overcome through dose adjustments ( 24 , 25 ), and the benefit accorded to patients through the early initiation of lenvatinib in combination with other anticancer therapies may outweigh the potential risks.…”

“…However, the potential for toxicity may also increase when combining several treatment modalities; furthermore, AEs are commonly reported with TKI treatment ( 24 , 25 ). Nonetheless, these may be overcome through dose adjustments ( 24 , 25 ), and the benefit accorded to patients through the early initiation of lenvatinib in combination with other anticancer therapies may outweigh the potential risks.…”

Efficacy and tolerability of initial low-dose lenvatinib to treat differentiated thyroid cancer

“…In clinical practice, the initial dose of lenvatinib is determined by the patient's characteristics. Suyama et al [15] reported that of 20 patients with DTC treated with lenvatinib, 5 started lenvatinib at an LD due to vessel invasion, trachea invasion, and advanced age. Berdelou et al [16] reported that of 75 patients, 54 started lenvatinib at a FD and 21 at an LD.…”