Adjuvant Antiangiogenic Agents in Post-nephrectomy Renal Cell Carcinoma

A Systematic Review and Meta-analysis

Mohamad B. Sonbol, Belal Firwana, Talal Hilal, Zhen Wang, Diana Almader-Douglas, Richard W Joseph, Thai H Ho

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)101-108
Number of pages8
JournalEuropean Urology Oncology
Volume1
Issue number2
DOIs
StatePublished - Jun 1 2018

Fingerprint

Angiogenesis Inhibitors
Nephrectomy
Renal Cell Carcinoma
Meta-Analysis
Disease-Free Survival
Placebos
Survival
Confidence Intervals
Randomized Controlled Trials
Recurrence
PubMed
Carcinoma
Safety

Keywords

  • Adjuvant chemotherapy
  • Pazopanib
  • Renal cell carcinoma
  • Sorafenib
  • Sunitinib
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Surgery
  • Oncology
  • Urology

Cite this

Adjuvant Antiangiogenic Agents in Post-nephrectomy Renal Cell Carcinoma : A Systematic Review and Meta-analysis. / Sonbol, Mohamad B.; Firwana, Belal; Hilal, Talal; Wang, Zhen; Almader-Douglas, Diana; Joseph, Richard W; Ho, Thai H.

In: European Urology Oncology, Vol. 1, No. 2, 01.06.2018, p. 101-108.

Research output: Contribution to journalReview article

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abstract = "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.",
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AU - Hilal, Talal

AU - Wang, Zhen

AU - Almader-Douglas, Diana

AU - Joseph, Richard W

AU - Ho, Thai H

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