Abstract | PURPOSE: In 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. METHODS: Adverse 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. RESULTS: The 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). CONCLUSIONS: In 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.
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Authors | Robert I Haddad, Martin Schlumberger, Lori J Wirth, Eric J Sherman, Manisha H Shah, Bruce Robinson, Corina E Dutcus, Angela Teng, Andrew G Gianoukakis, Steven I Sherman |
Journal | Endocrine
(Endocrine)
Vol. 56
Issue 1
Pg. 121-128
(Apr 2017)
ISSN: 1559-0100 [Electronic] United States |
PMID | 28155175
(Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)
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Chemical References |
- Antineoplastic Agents
- Phenylurea Compounds
- Quinolines
- lenvatinib
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Topics |
- Antineoplastic Agents
(adverse effects, therapeutic use)
- Diarrhea
(chemically induced, epidemiology)
- Disease-Free Survival
- Double-Blind Method
- Exanthema
(chemically induced, epidemiology)
- Fatigue
(chemically induced, epidemiology)
- Female
- Humans
- Incidence
- Male
- Phenylurea Compounds
(adverse effects, therapeutic use)
- Proteinuria
(chemically induced, epidemiology)
- Quinolines
(adverse effects, therapeutic use)
- Thyroid Neoplasms
(drug therapy, mortality, pathology)
- Treatment Outcome
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