PMID- 33981617
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220423
IS  - 2235-0640 (Print)
IS  - 2235-0802 (Electronic)
IS  - 2235-0640 (Linking)
VI  - 10
IP  - 2
DP  - 2021 Apr
TI  - Benefits and Limitations of TKIs in Patients with Medullary Thyroid Cancer: A 
      Systematic Review and Meta-Analysis.
PG  - 125-139
LID - 10.1159/000509457 [doi]
AB  - INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have been used in patients with 
      advanced medullary thyroid carcinoma (MTC); however, data on their effectiveness 
      and safety are limited. The aim of this systematic review and meta-analysis was 
      to document clinical response and toxicities of TKIs in advanced MTC. METHODS: We 
      systematically searched major databases for articles or abstracts on TKI use in 
      MTC patients until May 2018. Objective response (OR), defined as the sum of 
      complete + partial response, expressed as percentage, was our primary endpoint, 
      while disease stability, disease progression (DP), median progression-free 
      survival (PFS), and drug discontinuation rate due to adverse events (AEs) were 
      secondary endpoints. Pooled percentages, PFS time, and 95% CIs were reported. 
      RESULTS: Thirty-three publications were finally included in the analysis: 1 phase 
      IV, 2 phase III trials evaluating vandetanib and cabozantinib, respectively, 20 
      phase I or II studies, and the remaining 10 studies of 
      retrospective-observational nature. OR was documented in 28.6% (95% CI 25.9-31.9) 
      of patients. Stable disease was recorded in 46.2% (95% CI 43.3-49.1). Overall, DP 
      was observed in 22.9% (95% CI 20.4-27.6). Grade 3 or more AEs occurred in 48.5% 
      (95% CI 45.5-51.5) of patients, and drug discontinuation was reported in 44.7% 
      (95% CI 41.7-47.6). In general, use of TKIs conferred a PFS of 23.3 months (95% 
      CI 21.07-25.5). In particular, vandetanib induced an OR in 33.8% (95% CI 
      29.6-38.0) of patients and cabozantinib in 27.7% (95% CI 22.05-33.4). DP occurred 
      in 23.7% (95% CI 19.9-27.6) with vandetanib use and in 22.6% (95% CI 17.4-27.9) 
      in cabozantinib-treated patients. Sorafenib, the third most frequently studied 
      drug, showed intermediate efficacy, but higher discontinuation rates. CONCLUSION: 
      Treatment with TKIs in MTC patients with progressive disease is associated with a 
      moderate therapeutic benefit, with achievement of either disease stability or 
      partial response in 73%. The toxicity of these drugs is not negligible, but it 
      is, nonetheless, manageable.
CI  - Copyright (c) 2020 by S. Karger AG, Basel.
FAU - Efstathiadou, Zoe A
AU  - Efstathiadou ZA
AD  - Department of Endocrinology, "Hippokration" General Hospital of Thessaloniki, 
      Thessaloniki, Greece.
FAU - Tsentidis, Charalambos
AU  - Tsentidis C
AD  - Department of Endocrinology, General Hospital of Nikaia "Agios Panteleimon", 
      Piraeus, Greece.
FAU - Bargiota, Alexandra
AU  - Bargiota A
AD  - Department of Endocrinology, University of Thessaly, Larisa, Greece.
FAU - Daraki, Vasiliki
AU  - Daraki V
AD  - Department of Endocrinology, University Hospital of Crete, Heraklion, Greece.
FAU - Kotsa, Kalliopi
AU  - Kotsa K
AD  - Department of Endocrinology, "Ahepa" Hospital, Aristotle University, 
      Thessaloniki, Greece.
FAU - Ntali, Georgia
AU  - Ntali G
AD  - Department of Endocrinology, Diabetes and Metabolism, "Evangelismos" Hospital 
      Athens, Athens, Greece.
FAU - Papanastasiou, Labrini
AU  - Papanastasiou L
AD  - Department of Endocrinology and Diabetes Center, Athens General Hospital "G. 
      Gennimatas", Athens, Greece.
FAU - Tigas, Stelios
AU  - Tigas S
AD  - Department of Endocrinology, University of Ioannina, Ioannina, Greece.
FAU - Toulis, Konstantinos
AU  - Toulis K
AD  - Department of Endocrinology, 424 Military Hospital, Thessaloniki, Greece.
FAU - Pazaitou-Panayiotou, Kalliopi
AU  - Pazaitou-Panayiotou K
AD  - Division of Endocrinology, Endocrine Oncology, Interbalkan Medical Center, 
      Thessaloniki, Greece.
FAU - Alevizaki, Maria
AU  - Alevizaki M
AD  - Endocrine Unit, Department of Medical Therapeutics, School of Medicine, 
      Kapodistrian University of Athens, Athens, Greece.
LA  - eng
PT  - Journal Article
DEP - 20200911
PL  - England
TA  - Eur Thyroid J
JT  - European thyroid journal
JID - 101604579
PMC - PMC8077374
OTO - NOTNLM
OT  - Medullary thyroid cancer
OT  - Tyrosine kinase
OT  - Tyrosine kinase inhibitors
COIS- S.T. has participated in educational, research or advisory activities supported 
      by Amgen, Astra-Zeneca, Ipsen, Novartis, and Sanofi-Aventis. M.A. has served in 
      the advisory board for the use of vandetanib in MTC and has received lecture fees 
      from Sanofi. All other authors have no conflict of interest.
EDAT- 2021/05/14 06:00
MHDA- 2021/05/14 06:01
PMCR- 2021/10/01
CRDT- 2021/05/13 06:28
PHST- 2020/04/07 00:00 [received]
PHST- 2020/06/16 00:00 [accepted]
PHST- 2021/05/13 06:28 [entrez]
PHST- 2021/05/14 06:00 [pubmed]
PHST- 2021/05/14 06:01 [medline]
PHST- 2021/10/01 00:00 [pmc-release]
AID - etj-0010-0125 [pii]
AID - 10.1159/000509457 [doi]
PST - ppublish
SO  - Eur Thyroid J. 2021 Apr;10(2):125-139. doi: 10.1159/000509457. Epub 2020 Sep 11.