Poster Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Incidence and timing of common adverse events in lenvatinib-treated patients with radioiodine-refractory thyroid cancer from the SELECT trial (#427)

Robert Haddad 1 , Martin Schlumberger 2 , Lori J Wirth 3 , Eric J Sherman 4 , Manisha H Shah 5 , Bruce Robinson 6 , Corina E Dutcus 7 , Louise Young 8 , Angela Teng 7 , Andrew Gianoukakis 9 , Steven I Sherman 10
  1. Head and Neck Oncology Program, Harvard Medical School, Dana Farber Cancer Institute, Boston, Massachusetts, USA
  2. Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy and University of Paris-Sud, Villejuif, France
  3. Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
  4. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
  5. Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA
  6. Kolling Institute of Medical Research, University of Sydney, New South Wales, Australia
  7. Eisai Inc., Woodcliff Lake, New Jersey, USA
  8. Medical Department, Eisai Australia Pty Ltd., Melbourne, Australia
  9. Division of Endocrinology and Metabolism, Harbor-UCLA Medical Center, Torrance, California, USA
  10. Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA


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.