Lenvatinib (LEN) is approved for radioiodine-refractory differentiated thyroid cancer based on the phase 3 SELECT trial. Nearly all patients (pts) had an adverse event (AE; LEN vs placebo, respectively: any-grade, 100% vs 90%; grade 3, 72% vs 22%; grade 4, 12% vs 8%). We have previously reported an analysis of hypertension, management, and correlations with efficacy. Here we examine the 5 other most common LEN-emergent AEs in SELECT.
Pts received LEN (24 mg/d; 28-d cycle) or placebo. AEs were reported per Common Terminology Criteria for Adverse Events v4.0. Univariate analyses were performed for progression-free survival (PFS) and overall survival (OS); variables with P<0.2 were included in a multivariate analysis with baseline characteristics (Eastern Cooperative Oncology Group [ECOG] status, prior VEGF-targeted therapy, weight, age, region, and histology).
Among the most common LEN-emergent AEs (Table), there were no grade 4 events. Generally, AEs, while significant, occurred early in the course of treatment and were resolved (Table). Active management of these AEs (if any) was primarily with dose modifications. Treatment discontinuation due to AEs also occurred in 2 (1%) pts with proteinuria and 4 (2%) pts with fatigue. Multivariate analyses showed no significant associations between these 5 AEs and PFS. In a multivariate analysis, ECOG status (P=0.001), histology (favoring follicular vs papillary, P=0.002), and any-grade diarrhea (P=0.023) were found to be significantly associated with OS (median OS for LEN-treated pts with diarrhea: not reached; without: 17.1 months).
In SELECT, LEN-emergent AEs typically occurred early during the course of treatment, and were primarily managed with dose modifications. A significant association between OS and diarrhea was found.
PPES, palmar-plantar erythrodysesthesia syndrome; Q, quartile.