TY - JOUR
T1 - Adjuvant Antiangiogenic Agents in Post-nephrectomy Renal Cell Carcinoma
T2 - A Systematic Review and Meta-analysis
AU - Sonbol, Mohamad B.
AU - Firwana, Belal
AU - Hilal, Talal
AU - Wang, Zhen
AU - Almader-Douglas, Diana
AU - Joseph, Richard W.
AU - Ho, Thai H.
N1 - Funding Information:
Acknowledgments: We acknowledge the support provided by the Gloria A. and Thomas J. Dutson Jr. Kidney Research Endowment. This work was supported by a Gerstner Family Career Development Award (T.H.H.) and Department of Defense grant W81XWH-17-1-0546 (T.H.H.). The opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense.
Publisher Copyright:
© 2018 European Association of Urology
PY - 2018/6
Y1 - 2018/6
N2 - Context: The role of antiangiogenic agents in advanced renal cell carcinoma (RCC) is well established. However, it is still not clear whether this benefit can be extrapolated to the adjuvant setting. Objective: To determine the efficacy and safety of antiangiogenic agents in patients with RCC and a high risk of relapse after nephrectomy. Evidence acquisition: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) evaluating the use of any oral antiangiogenic agent compared to placebo in post-nephrectomy RCC patients. Prespecified data elements were extracted from each trial. Outcomes of interest included overall survival (OS) and disease-free survival (DFS). The overall effect was pooled using the DerSimonian and Laird random-effects models. Evidence synthesis: Three RCTs comparing antiangiogenics to placebo among 3693 patients met our inclusion criteria and were used in meta-analyses. Overall, antiangiogenics did not improve DFS (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.78–1.07) or OS (HR 0.99, 95% CI 0.79–1.25). These results persisted when restricting the analysis to patients with clear cell carcinoma and patients with highest risk of relapse. Similarly, sunitinib did not show any improvement in the entire cohort for either DFS (HR 0.89, 95% CI 0.67–1.19) or OS (HR 1.11, 95% CI 0.90–1.37). Conclusions: In this meta-analysis, antiangiogenics did not improve OS and DFS over placebo in high-risk RCC after nephrectomy. Further studies are needed to identify the patient population that might derive a benefit from antiangiogenics in the adjuvant setting. Patient summary: In this article, we found that there is currently insufficient evidence to support the use of oral antiangiogenics in nonmetastatic renal cell carcinoma after nephrectomy. In addition, the use of oral antiangiogenics was associated with a 2.7-fold higher rate of significant side effects compared to placebo. In this article, we found that adjuvant use of antiangiogenics does not improve survival and was associated with 2.7-fold higher risk of significant toxicities. Currently, there is insufficient evidence that the use of antiangiogenics would enhance cure in renal cell carcinoma patients after nephrectomy.
AB - Context: The role of antiangiogenic agents in advanced renal cell carcinoma (RCC) is well established. However, it is still not clear whether this benefit can be extrapolated to the adjuvant setting. Objective: To determine the efficacy and safety of antiangiogenic agents in patients with RCC and a high risk of relapse after nephrectomy. Evidence acquisition: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) evaluating the use of any oral antiangiogenic agent compared to placebo in post-nephrectomy RCC patients. Prespecified data elements were extracted from each trial. Outcomes of interest included overall survival (OS) and disease-free survival (DFS). The overall effect was pooled using the DerSimonian and Laird random-effects models. Evidence synthesis: Three RCTs comparing antiangiogenics to placebo among 3693 patients met our inclusion criteria and were used in meta-analyses. Overall, antiangiogenics did not improve DFS (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.78–1.07) or OS (HR 0.99, 95% CI 0.79–1.25). These results persisted when restricting the analysis to patients with clear cell carcinoma and patients with highest risk of relapse. Similarly, sunitinib did not show any improvement in the entire cohort for either DFS (HR 0.89, 95% CI 0.67–1.19) or OS (HR 1.11, 95% CI 0.90–1.37). Conclusions: In this meta-analysis, antiangiogenics did not improve OS and DFS over placebo in high-risk RCC after nephrectomy. Further studies are needed to identify the patient population that might derive a benefit from antiangiogenics in the adjuvant setting. Patient summary: In this article, we found that there is currently insufficient evidence to support the use of oral antiangiogenics in nonmetastatic renal cell carcinoma after nephrectomy. In addition, the use of oral antiangiogenics was associated with a 2.7-fold higher rate of significant side effects compared to placebo. In this article, we found that adjuvant use of antiangiogenics does not improve survival and was associated with 2.7-fold higher risk of significant toxicities. Currently, there is insufficient evidence that the use of antiangiogenics would enhance cure in renal cell carcinoma patients after nephrectomy.
KW - Adjuvant chemotherapy
KW - Pazopanib
KW - Renal cell carcinoma
KW - Sorafenib
KW - Sunitinib
KW - Tyrosine kinase inhibitors
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U2 - 10.1016/j.euo.2018.03.012
DO - 10.1016/j.euo.2018.03.012
M3 - Review article
C2 - 30345423
AN - SCOPUS:85067230028
SN - 2588-9311
VL - 1
SP - 101
EP - 108
JO - European Urology Oncology
JF - European Urology Oncology
IS - 2
ER -