Adjuvant Therapy in High-Risk Renal Cell Cancer

A Systematic Review and Meta-analysis

Irbaz B. Riaz, W. Faridi, Muhammad Husnain, Saad Ullah Malik, Qurat Ul Ain R. Sipra, Farva R. Gondal, Hao Xie, Siddhartha Yadav, Manish Kohli

Research output: Contribution to journalArticle

Abstract

Objective: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating risk-benefit for adjuvant postoperative treatments in high-risk renal cell carcinoma by assessing reported disease-free survival (DFS), overall survival (OS), toxicity, and quality of life. Methods: A literature search was performed in PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials to identify relevant RCTs (from database inception through May 15, 2018). The results of the ATLAS trial were published while writing this manuscript, and the manuscript was updated accordingly. A generic variance-weighted random effects model was used to derive estimates for efficacy and common adverse effects. Heterogeneity was assessed using the Cochran Q statistic and was quantified using the I2 test. Results: Adjuvant therapy with tyrosine kinase inhibitors compared with placebo was observed to have a DFS hazard ratio [HR] of 0.92 (95% CI, 0.83-1.01) and an OS HR of 1.01 (95% CI, 0.89-1.15) (4 RCTs; 4417 patients). Analysis of DFS for sunitinib compared with placebo (n=1909) in the adjuvant setting detected an HR of 0.90 (95% CI, 0.67-1.19). Increased risk of grade 3 or 4 adverse events (relative risk [RR]=2.6; 95% CI, 2.28-2.97), diarrhea (RR=9.89; 95% CI, 4.22-23.14), fatigue (RR=3.11; 95% CI, 1.86-5.18), hypertension (RR=3.63; 95% CI, 2.99-4.41), and palmar/plantar dysesthesia (RR=2.70; 95% CI, 2.47-2.96) was observed. Conclusion: Adjuvant vascular endothelial growth factor tyrosine kinase inhibitors in high-risk renal cell carcinoma did not improve OS or DFS, and there was a significant increased risk of toxicity in greater than half of the patients, leading to a decline in quality of life.

Original languageEnglish (US)
Pages (from-to)1524-1534
Number of pages11
JournalMayo Clinic proceedings
Volume94
Issue number8
DOIs
StatePublished - Aug 1 2019

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Renal Cell Carcinoma
Meta-Analysis
Disease-Free Survival
Therapeutics
Randomized Controlled Trials
Protein-Tyrosine Kinases
Survival
Placebos
Quality of Life
Manuscripts
Paresthesia
PubMed
Vascular Endothelial Growth Factor A
Fatigue
Diarrhea
Databases
Hypertension

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Riaz, I. B., Faridi, W., Husnain, M., Malik, S. U., Sipra, Q. U. A. R., Gondal, F. R., ... Kohli, M. (2019). Adjuvant Therapy in High-Risk Renal Cell Cancer: A Systematic Review and Meta-analysis. Mayo Clinic proceedings, 94(8), 1524-1534. https://doi.org/10.1016/j.mayocp.2019.01.045

Adjuvant Therapy in High-Risk Renal Cell Cancer : A Systematic Review and Meta-analysis. / Riaz, Irbaz B.; Faridi, W.; Husnain, Muhammad; Malik, Saad Ullah; Sipra, Qurat Ul Ain R.; Gondal, Farva R.; Xie, Hao; Yadav, Siddhartha; Kohli, Manish.

In: Mayo Clinic proceedings, Vol. 94, No. 8, 01.08.2019, p. 1524-1534.

Research output: Contribution to journalArticle

Riaz, IB, Faridi, W, Husnain, M, Malik, SU, Sipra, QUAR, Gondal, FR, Xie, H, Yadav, S & Kohli, M 2019, 'Adjuvant Therapy in High-Risk Renal Cell Cancer: A Systematic Review and Meta-analysis', Mayo Clinic proceedings, vol. 94, no. 8, pp. 1524-1534. https://doi.org/10.1016/j.mayocp.2019.01.045
Riaz, Irbaz B. ; Faridi, W. ; Husnain, Muhammad ; Malik, Saad Ullah ; Sipra, Qurat Ul Ain R. ; Gondal, Farva R. ; Xie, Hao ; Yadav, Siddhartha ; Kohli, Manish. / Adjuvant Therapy in High-Risk Renal Cell Cancer : A Systematic Review and Meta-analysis. In: Mayo Clinic proceedings. 2019 ; Vol. 94, No. 8. pp. 1524-1534.
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abstract = "Objective: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating risk-benefit for adjuvant postoperative treatments in high-risk renal cell carcinoma by assessing reported disease-free survival (DFS), overall survival (OS), toxicity, and quality of life. Methods: A literature search was performed in PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials to identify relevant RCTs (from database inception through May 15, 2018). The results of the ATLAS trial were published while writing this manuscript, and the manuscript was updated accordingly. A generic variance-weighted random effects model was used to derive estimates for efficacy and common adverse effects. Heterogeneity was assessed using the Cochran Q statistic and was quantified using the I2 test. Results: Adjuvant therapy with tyrosine kinase inhibitors compared with placebo was observed to have a DFS hazard ratio [HR] of 0.92 (95{\%} CI, 0.83-1.01) and an OS HR of 1.01 (95{\%} CI, 0.89-1.15) (4 RCTs; 4417 patients). Analysis of DFS for sunitinib compared with placebo (n=1909) in the adjuvant setting detected an HR of 0.90 (95{\%} CI, 0.67-1.19). Increased risk of grade 3 or 4 adverse events (relative risk [RR]=2.6; 95{\%} CI, 2.28-2.97), diarrhea (RR=9.89; 95{\%} CI, 4.22-23.14), fatigue (RR=3.11; 95{\%} CI, 1.86-5.18), hypertension (RR=3.63; 95{\%} CI, 2.99-4.41), and palmar/plantar dysesthesia (RR=2.70; 95{\%} CI, 2.47-2.96) was observed. Conclusion: Adjuvant vascular endothelial growth factor tyrosine kinase inhibitors in high-risk renal cell carcinoma did not improve OS or DFS, and there was a significant increased risk of toxicity in greater than half of the patients, leading to a decline in quality of life.",
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AU - Malik, Saad Ullah

AU - Sipra, Qurat Ul Ain R.

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