Everolimus and temsirolimus are not the same second-line in metastatic renal cell carcinoma. A systematic review and meta-analysis of literature data

Roberto Iacovelli, Matteo Santoni, Elena Verzoni, Paolo Grassi, Isabella Testa, Filippo De Braud, Stefano Cascinu, Giuseppe Procopio

Research output: Contribution to journalArticle

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 χ2 test, and inconsistency was quantified with the I2 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.

Original languageEnglish
Pages (from-to)137-141
Number of pages5
JournalClinical Genitourinary Cancer
Volume13
Issue number2
DOIs
Publication statusPublished - Apr 1 2015

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Treatment Failure
Renal Cell Carcinoma
Meta-Analysis
Publication Bias
Confidence Intervals
Vascular Endothelial Growth Factor Receptor
Survival
Therapeutics
PubMed
MEDLINE
Protein-Tyrosine Kinases
Databases
temsirolimus
Everolimus
Population

Keywords

  • inhibitors
  • mRCC
  • mTOR
  • Second-line
  • Sequence of therapy

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Medicine(all)

Cite this

Everolimus and temsirolimus are not the same second-line in metastatic renal cell carcinoma. A systematic review and meta-analysis of literature data. / Iacovelli, Roberto; Santoni, Matteo; Verzoni, Elena; Grassi, Paolo; Testa, Isabella; De Braud, Filippo; Cascinu, Stefano; Procopio, Giuseppe.

In: Clinical Genitourinary Cancer, Vol. 13, No. 2, 01.04.2015, p. 137-141.

Research output: Contribution to journalArticle

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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 χ2 test, and inconsistency was quantified with the I2 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.",
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T1 - Everolimus and temsirolimus are not the same second-line in metastatic renal cell carcinoma. A systematic review and meta-analysis of literature data

AU - Iacovelli, Roberto

AU - Santoni, Matteo

AU - Verzoni, Elena

AU - Grassi, Paolo

AU - Testa, Isabella

AU - De Braud, Filippo

AU - Cascinu, Stefano

AU - Procopio, Giuseppe

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AB - 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 χ2 test, and inconsistency was quantified with the I2 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.

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