PMID- 30471649
OWN - NLM
STAT- MEDLINE
DCOM- 20200504
LR  - 20200505
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 106
DP  - 2019 Jan
TI  - Impact of dose interruption on the efficacy of lenvatinib in a phase 3 study in 
      patients with radioiodine-refractory differentiated thyroid cancer.
PG  - 61-68
LID - S0959-8049(18)31430-8 [pii]
LID - 10.1016/j.ejca.2018.10.002 [doi]
AB  - BACKGROUND: In the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer 
      of the Thyroid (SELECT), lenvatinib significantly improved efficacy outcomes 
      versus placebo in patients with radioiodine-refractory differentiated thyroid 
      cancer (RR-DTC). Lenvatinib-treated patients had more adverse events (AEs), which 
      were generally managed with dose modifications, including dose interruption. This 
      exploratory post hoc analysis investigated the impact of dose interruption on 
      lenvatinib efficacy. METHODS: Dose modifications were required for grade 3 or 
      intolerable grade 2 AEs in SELECT. Lenvatinib-treated patients were dichotomised 
      based on the duration of dose interruption relative to total treatment duration: 
      shorter dose interruption (<10% of total treatment duration) and longer dose 
      interruption (>/=10%). RESULTS: At the time of primary data cut-off (November 15, 
      2013; median follow-up, 17.1 months), the median progression-free survival (PFS) 
      for the shorter dose-interruption group had not yet been reached, whereas median 
      PFS for the longer dose-interruption group was 12.8 months (95% confidence 
      interval [CI], 9.3-16.5). Compared with placebo, the hazard ratios for PFS in the 
      shorter and longer dose-interruption groups were 0.14 (95% CI, 0.09-0.20) and 
      0.31 (95% CI, 0.22-0.43), respectively. In a multivariate model, dose 
      interruption was significantly associated with lenvatinib efficacy, even after 
      adjustment for patient characteristics. CONCLUSIONS: Lenvatinib improved efficacy 
      outcomes versus placebo in patients with RR-DTC, regardless of the duration of 
      dose interruption; however, those with shorter dose interruptions had a greater 
      magnitude of benefit versus those with longer interruptions. This analysis 
      highlights the importance of timely management of lenvatinib toxicities to 
      minimise dose interruptions and maximise lenvatinib efficacy in patients with 
      RR-DTC. CLINICALTRIALS. GOV NUMBER: NCT01321554.
CI  - Copyright (c) 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Tahara, Makoto
AU  - Tahara M
AD  - National Cancer Centre Hospital East, Kashiwa, Chiba, Japan. Electronic address: 
      matahara@east.ncc.go.jp.
FAU - Brose, Marcia S
AU  - Brose MS
AD  - Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
FAU - Wirth, Lori J
AU  - Wirth LJ
AD  - Massachusetts General Hospital, Harvard University, Boston, MA, USA.
FAU - Suzuki, Takuya
AU  - Suzuki T
AD  - Eisai Co., Ltd., Tokyo, Japan.
FAU - Miyagishi, Hideaki
AU  - Miyagishi H
AD  - Eisai Co., Ltd., Tokyo, Japan.
FAU - Fujino, Katsuki
AU  - Fujino K
AD  - Eisai Co., Ltd., Tokyo, Japan.
FAU - Dutcus, Corina E
AU  - Dutcus CE
AD  - Eisai Inc., Woodcliff Lake, NJ, USA.
FAU - Gianoukakis, Andrew
AU  - Gianoukakis A
AD  - Los Angeles Biomedical Research Institute and Division of Endocrinology and 
      Metabolism, Harbor-UCLA Medical Center, Torrance, CA, USA; David Geffen School of 
      Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01321554
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20181122
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinolines)
RN  - EE083865G2 (lenvatinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*administration & dosage/adverse effects
MH  - Cell Differentiation
MH  - Disease Progression
MH  - Disease-Free Survival
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Iodine Radioisotopes/adverse effects/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Phenylurea Compounds/*administration & dosage/adverse effects
MH  - Protein Kinase Inhibitors/*administration & dosage/adverse effects
MH  - Quinolines/*administration & dosage/adverse effects
MH  - *Radiation Tolerance
MH  - Risk Assessment
MH  - Risk Factors
MH  - Thyroid Neoplasms/mortality/pathology/*therapy
MH  - Time Factors
OTO - NOTNLM
OT  - Disease-free survival
OT  - Lenvatinib
OT  - MeSH terms
OT  - Thyroid neoplasms
EDAT- 2018/11/25 06:00
MHDA- 2020/05/06 06:00
CRDT- 2018/11/25 06:00
PHST- 2018/08/01 00:00 [received]
PHST- 2018/09/21 00:00 [revised]
PHST- 2018/10/09 00:00 [accepted]
PHST- 2018/11/25 06:00 [pubmed]
PHST- 2020/05/06 06:00 [medline]
PHST- 2018/11/25 06:00 [entrez]
AID - S0959-8049(18)31430-8 [pii]
AID - 10.1016/j.ejca.2018.10.002 [doi]
PST - ppublish
SO  - Eur J Cancer. 2019 Jan;106:61-68. doi: 10.1016/j.ejca.2018.10.002. Epub 2018 Nov 
      22.