Abstract | AIM: METHODS: Searching the MEDLINE/PubMed, Cochrane Library and American Society of Clinical Oncology Meeting abstracts prospective studies were identified. Data extraction was conduced according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The measured outcomes were progression-free survival (PFS), overall survival (OS) and the overall response rate (ORR). RESULTS: Four randomised controlled trials were selected for final analysis, with a total of 332 patients evaluable for PFS. Treatment with TKi significantly reduced the risk of progression compared with mTORi (hazard ratio [HR] = 0.71; 95% confidence interval [CI] 0.60-0.84; p < 0.0001). This difference remained significant when sunitinib was compared with everolimus in first-line setting (HR = 0.67; 95% CI, 0.56-0.80; p < 0.00001). In the 332 patients evaluable for OS, no significant difference was found between TKi and mTORi (HR = 0.86; 95% CI, 0.67-1.12; p = 0.27). In the 176 evaluable patients, TKis therapy did not improve the ORR when compared with mTORi (relative risk [RR] = 2.21; 95% CI, 0.87-5.60; p = 0.09), even if treatment with sunitinib doubled the probability of achieving a tumour response. CONCLUSIONS: Treatment with TKis significantly improves PFS, but not OS, when compared with mTORi. Moreover, sunitinib as first-line therapy reduces the risk of progression compared with everolimus; therefore, supporting the standard treatment paradigm broadly used for ccRCC patients. The relatively modest efficacy of available targeted therapies reinforces the need of future histology based, molecular driven therapeutic paradigm.
|
Authors | Chiara Ciccarese, Roberto Iacovelli, Matteo Brunelli, Francesco Massari, Davide Bimbatti, Emanuela Fantinel, Vincenzo De Marco, Antonio Benito Porcaro, Guido Martignoni, Walter Artibani, Giampaolo Tortora |
Journal | European journal of cancer (Oxford, England : 1990)
(Eur J Cancer)
Vol. 83
Pg. 237-246
(09 2017)
ISSN: 1879-0852 [Electronic] England |
PMID | 28756136
(Publication Type: Journal Article, Meta-Analysis, Review)
|
Copyright | Copyright © 2017 Elsevier Ltd. All rights reserved. |
Chemical References |
- Protein Kinase Inhibitors
- Vascular Endothelial Growth Factor A
- MTOR protein, human
- Protein-Tyrosine Kinases
- TOR Serine-Threonine Kinases
|
Topics |
- Carcinoma, Renal Cell
(drug therapy)
- Clinical Trials as Topic
- Disease-Free Survival
- Humans
- Kidney Neoplasms
(drug therapy)
- Prospective Studies
- Protein Kinase Inhibitors
(therapeutic use)
- Protein-Tyrosine Kinases
(antagonists & inhibitors)
- TOR Serine-Threonine Kinases
(antagonists & inhibitors)
- Vascular Endothelial Growth Factor A
(antagonists & inhibitors)
|