Roberto Iacovelli1, Matteo Santoni2, Elena Verzoni3, Paolo Grassi3, Isabella Testa3, Filippo de Braud3, Stefano Cascinu2, Giuseppe Procopio3. 1. Fondazione IRCCS Istituto Nazionale Tumori, Department of Medical Oncology, Milan, Italy. Electronic address: roberto.iacovelli@istitutotumori.mi.it. 2. Università Politecnica delle Marche, AOU Ospedali Riuniti, Department of Medical Oncology, Ancona, Italy. 3. Fondazione IRCCS Istituto Nazionale Tumori, Department of Medical Oncology, Milan, Italy.
Abstract
BACKGROUND: Two mTOR inhibitors, TEM and EVE, proved to be active in mRCC but have never been compared in a prospective trial. We aimed to compare their effectiveness in mRCC patients previously treated with a vascular endothelial growth factor receptor tyrosine kinase inhibitor, and performed a systematic review and meta-analysis of available evidence. MATERIALS AND METHODS: The MEDLINE/PubMed database was reviewed for studies that compared EVE with TEM from January 2006 to May 2014. Summary hazard ratio (HR) for overall survival (OS) and time to treatment failure (TTF) were calculated using random and fixed effects models depending on the heterogeneity of included studies. Statistical heterogeneity was assessed using the χ(2) test, and inconsistency was quantified with the I(2) statistic. Publication bias was evaluated using the Begg and Egger test. RESULTS: Four studies were included in the meta-analysis; data of 937 patients were available: 545 received EVE and 392 TEM. Among the included patients, 863 [92%] were treated with sunitinib and 74 [8%] with pazopanib or sorafenib as first-line therapy. In the overall population, treatment with EVE decreased the risk of death by 26% over TEM (HR, 0.74; 95% confidence interval [CI], 0.59-0.93; P = .008). The TTF was evaluable in 692 patients; in this group, treatment with EVE decreased the risk of treatment failure by 30% (HR, 0.70; 95% CI, 0.56-0.88; P = .002). No significant heterogeneity or publication bias was found for OS and TTF. CONCLUSION: In this analysis, we compared EVE with TEM as second-line therapy in mRCC, and report a significant difference between mTOR inhibitors, even if these results need to be confirmed in a prospective trial.
BACKGROUND: Two mTOR inhibitors, TEM and EVE, proved to be active in mRCC but have never been compared in a prospective trial. We aimed to compare their effectiveness in mRCC patients previously treated with a vascular endothelial growth factor receptor tyrosine kinase inhibitor, and performed a systematic review and meta-analysis of available evidence. MATERIALS AND METHODS: The MEDLINE/PubMed database was reviewed for studies that compared EVE with TEM from January 2006 to May 2014. Summary hazard ratio (HR) for overall survival (OS) and time to treatment failure (TTF) were calculated using random and fixed effects models depending on the heterogeneity of included studies. Statistical heterogeneity was assessed using the χ(2) test, and inconsistency was quantified with the I(2) statistic. Publication bias was evaluated using the Begg and Egger test. RESULTS: Four studies were included in the meta-analysis; data of 937 patients were available: 545 received EVE and 392 TEM. Among the included patients, 863 [92%] were treated with sunitinib and 74 [8%] with pazopanib or sorafenib as first-line therapy. In the overall population, treatment with EVE decreased the risk of death by 26% over TEM (HR, 0.74; 95% confidence interval [CI], 0.59-0.93; P = .008). The TTF was evaluable in 692 patients; in this group, treatment with EVE decreased the risk of treatment failure by 30% (HR, 0.70; 95% CI, 0.56-0.88; P = .002). No significant heterogeneity or publication bias was found for OS and TTF. CONCLUSION: In this analysis, we compared EVE with TEM as second-line therapy in mRCC, and report a significant difference between mTOR inhibitors, even if these results need to be confirmed in a prospective trial.
Authors: I Duran; J Lambea; P Maroto; J L González-Larriba; Luis Flores; S Granados-Principal; M Graupera; B Sáez; A Vivancos; O Casanovas Journal: Target Oncol Date: 2017-02 Impact factor: 4.493
Authors: Ethan A Ferrel; Andrew T Roehrig; Erin A Kaya; Jonathan D Carlson; Benjamin C Ling; Aaron Wagner; Alexander R MacKay; Jason A Call; John J Demakas; Wayne T Lamoreaux; Robert K Fairbanks; Barton S Cooke; Ben Peressini; Christopher M Lee Journal: Int J Mol Sci Date: 2016-03-18 Impact factor: 5.923