PMID- 31838709
OWN - NLM
STAT- MEDLINE
DCOM- 20200928
LR  - 20231103
IS  - 1865-8652 (Electronic)
IS  - 0741-238X (Print)
IS  - 0741-238X (Linking)
VI  - 37
IP  - 2
DP  - 2020 Feb
TI  - Efficacy and Safety of Approved First-Line Tyrosine Kinase Inhibitor Treatments 
      in Metastatic Renal Cell Carcinoma: A Network Meta-Analysis.
PG  - 730-744
LID - 10.1007/s12325-019-01167-2 [doi]
AB  - INTRODUCTION: This network meta-analysis aims to deliver an up-to-date, 
      comprehensive efficacy and toxicity comparison of the approved first-line 
      tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC) in 
      order to provide support for evidence-based treatment decisions. Previous NMAs of 
      first-line mRCC treatments either predate the approval of all the first-line TKIs 
      currently available or do not include evaluation of safety data for all 
      treatments. METHODS: We performed a systematic literature review and network 
      meta-analysis of phase II/III randomised controlled trials (RCTs) assessing 
      approved first-line TKI therapies for mRCC. A random effects model with a 
      frequentist approach was computed for progression-free survival (PFS) data and 
      for the proportion of patients experiencing a maximum of grade 3 or 4 adverse 
      events (AEs). RESULTS: The network meta-analysis of PFS demonstrated no 
      significant differences between cabozantinib and either sunitinib (50 mg 4/2), 
      pazopanib or tivozanib. The network meta-analysis indicated that in terms of 
      grade 3 and 4 AEs, tivozanib had the most favourable safety profile and was 
      associated with significantly less risk of toxicity than the other TKIs. 
      CONCLUSION: These network meta-analysis data demonstrate that cabozantinib, 
      sunitinib, pazopanib and tivozanib do not significantly differ in their efficacy, 
      but tivozanib is associated with a more favourable safety profile in terms of 
      grade 3 or 4 toxicities. Consequently, the relative toxicity of these first-line 
      TKIs may play a more significant role than efficacy comparisons in treatment 
      decisions and in planning future RCTs.
FAU - Manz, Kirsi M
AU  - Manz KM
AD  - Institut fur Medizinische Informationsverarbeitung, Biometrie und Epidemiologie 
      (IBE), LMU Munich, Munich, Germany.
FAU - Fenchel, Klaus
AU  - Fenchel K
AD  - Department of Haematology and Oncology, Medical School Hamburg (MSH), Hamburg, 
      Germany.
FAU - Eilers, Andreas
AU  - Eilers A
AD  - EUSA Pharma Ltd, Hemel Hempstead, UK.
FAU - Morgan, Jonathan
AU  - Morgan J
AD  - EUSA Pharma Ltd, Hemel Hempstead, UK.
FAU - Wittling, Kirsten
AU  - Wittling K
AD  - EUSA Pharma Ltd, Hemel Hempstead, UK.
FAU - Dempke, Wolfram C M
AU  - Dempke WCM
AUID- ORCID: 0000-0002-7683-1017
AD  - Department of Haematology and Oncology, University Clinic, LMU Munich, Munich, 
      Germany. wolfram.dempke@web.de.
LA  - eng
SI  - figshare/10.6084/m9.figshare.11110208
PT  - Comparative Study
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
DEP - 20191214
PL  - United States
TA  - Adv Ther
JT  - Advances in therapy
JID - 8611864
RN  - 0 (Anilides)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridines)
RN  - 0 (Pyrimidines)
RN  - 0 (Quinolines)
RN  - 0 (Sulfonamides)
RN  - 1C39JW444G (cabozantinib)
RN  - V99T50803M (Sunitinib)
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anilides/therapeutic use
MH  - Antineoplastic Agents/*therapeutic use
MH  - Carcinoma, Renal Cell/*drug therapy
MH  - Female
MH  - Humans
MH  - Kidney Neoplasms/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis/*drug therapy
MH  - Network Meta-Analysis
MH  - Phenylurea Compounds/therapeutic use
MH  - Progression-Free Survival
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Pyridines/therapeutic use
MH  - Pyrimidines/therapeutic use
MH  - Quinolines/therapeutic use
MH  - Sulfonamides/therapeutic use
MH  - Sunitinib/*therapeutic use
PMC - PMC7004428
OTO - NOTNLM
OT  - Adverse event
OT  - Metastatic renal cell carcinoma
OT  - Network meta-analysis
OT  - Progression-free survival
OT  - Randomised controlled trials
OT  - Tyrosine kinase inhibitors
EDAT- 2019/12/16 06:00
MHDA- 2020/09/29 06:00
PMCR- 2019/12/14
CRDT- 2019/12/16 06:00
PHST- 2019/09/30 00:00 [received]
PHST- 2019/12/16 06:00 [pubmed]
PHST- 2020/09/29 06:00 [medline]
PHST- 2019/12/16 06:00 [entrez]
PHST- 2019/12/14 00:00 [pmc-release]
AID - 10.1007/s12325-019-01167-2 [pii]
AID - 1167 [pii]
AID - 10.1007/s12325-019-01167-2 [doi]
PST - ppublish
SO  - Adv Ther. 2020 Feb;37(2):730-744. doi: 10.1007/s12325-019-01167-2. Epub 2019 Dec 
      14.