Incidence and timing of common adverse events in Lenvatinib-treated patients from the SELECT trial and their association with survival outcomes

Abstract

PurposeIn the study of (E7080) lenvatinib in differentiated cancer of the thyroid, most patients experienced an adverse event. In this report, we examine common lenvatinib-emergent adverse events in this phase three, randomized, double-blind study.MethodsAdverse events were graded per Common Terminology Criteria for Adverse Events v4.0. 392 patients were enrolled (lenvatinib: 261, placebo: 131) and received lenvatinib 24 mg/day or placebo. The main outcome measures were: associations with progression-free survival and overall survival in exploratory univariate and multivariate analyses along with additional variables.ResultsThe most common any-grade adverse events (any grade; grade 3) in lenvatinib-treated patients included proteinuria (32%; 10%), diarrhea (67%; 9%), fatigue/asthenia/malaise (67%; 10%), rash (23%; 0.4%), and palmar-plantar erythrodysesthesia syndrome (33%; 3%). There were no grade 4 events for these adverse events. They generally occurred early (median time to first onset [weeks]: proteinuria [6.1], diarrhea [12.1], fatigue/asthenia/malaise [3.0], rash [7.3], and palmar-plantar erythrodysesthesia syndrome [5.9]), and were resolved primarily with dose modifications (median time to resolution [weeks]: proteinuria [8.8], diarrhea [18.1], fatigue/asthenia/malaise [16.3], rash [5.9], and palmar-plantar erythrodysesthesia syndrome [20.0]). Discontinuation due to these adverse events occurred in 2 (1%) patients with proteinuria and 4 (2%) with fatigue. Progression-free survival was not associated with any of the adverse events. Eastern Cooperative Oncology Group performance status (P = 0.001), follicular histology (P = 0.002), and diarrhea (P = 0.023) were associated with overall survival in multivariate analyses (median overall survival for patients with diarrhea: not reached; without: 17.1 months).ConclusionsIn the study of (E7080) lenvatinib in differentiated cancer of the thyroid, the most common adverse events typically occurred early and were primarily managed with dose modifications. Overall survival was significantly associated with diarrhea.

Optimal use of lenvatinib in the treatment of advanced thyroid cancer

“…However, the incidences of grade ≥ 3 were similar (3.3% in Japanese patients and 3.4% in the general population) [2,7]. The median time to first onset was 5.9 weeks [20].…”

“…Diarrhea was generally mild, of grade 1 or 2 in severity. The median time to first onset was 12.1 weeks [20]. Supportive therapy is needed to prevent dehydration, and an antidiarrheal agent such as loperamide should be considered.…”

“…Onset of fatigue was seen early after initiation of lenvatinib, with a median time to first onset of 3 weeks [20]. Treatment interruption is recommended if patients experience intolerable fatigue.…”

Novel approaches for molecular targeted therapy against hepatocellular carcinoma

“…Proteinuria develops relatively early and its median onset time after the initiation of lenvatinib is 6.1 weeks. 57 Anti-angiogenic treatments blocking VEGF are associated with the occurrence of proteinuria. [58][59][60] Additionally, FGFR inhibition can adversely affect podocyte function in TKI-treated patients.…”

PharmaForum Eisai

“…Andere Studien belegten, dass UE mit einem besseren klinischen Outcome assoziiert sein können [3]. Bei Patienten mit radiorefraktärem Schilddrüsenkarzinom, die mit Lenvatinib behandelt wurden, war eine behandlungsbedingte Hypertonie signifikant mit einer besseren Wirksamkeit verbunden [7], eine behandlungsbedingte Diarrhö mit einem verbesserten OS [8].…”