Adjuvant Vascular Endothelial Growth Factor-targeted Therapy in Renal Cell Carcinoma: A Systematic Review and Pooled Analysis

Contradictory data exist with regard to adjuvant vascular endothelial growth factor receptor (VEGFR)-targeted therapy in surgically managed patients for localized renal cell carcinoma (RCC).

To systematically evaluate the current evidence regarding the therapeutic benefit (disease-free survival [DFS] and overall survival [OS]) and grade 3-4 adverse events (AEs) for adjuvant VEGFR-targeted therapy for resected localized RCC.

A critical review of PubMed/Medline, Embase, and the Cochrane Library in January 2018 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement was performed. We identified reports and reviewed them according to the Consolidated Standards of Reporting Trials and Standards for the Reporting of Diagnostic Accuracy Studies criteria. Of eight full-text articles that were eligible for inclusion, five studies (two of five were updated analyses) were retained in the final synthesis. Study characteristics were abstracted and the number needed to treat (NNT) per trial was estimated.

The three randomized controlled phase III trials included the following comparisons: sunitinib versus placebo or sorafenib versus placebo (Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma [ASSURE] study, n=1943), sunitinib versus placebo (S-TRAC, n=615), and pazopanib versus placebo (Pazopanib As Adjuvant Therapy in Localized/Locally Advanced RCC After Nephrectomy study, n=1135). The NNT ranged from 10 (S-TRAC) to 137 (ASSURE study). The pooled analysis showed that VEGFR-targeted therapy was not statistically significantly associated with improved DFS (hazard ratio [HRrandom]: 0.92, 95% confidence interval [CI]: 0.82-1.03, p=0.16) or OS (HRrandom: 0.98, 95% CI: 0.84-1.15, p=0.84) compared with the control group. The adjuvant therapy group experienced significantly higher odds of grade 3-4 AEs (ORrandom: 5.89, 95% CI: 4.85-7.15, p<0.001). In exploratory analyses focusing on patients who started on the full-dose regimen, DFS was improved in patients who received adjuvant therapy (HRrandom: 0.83, 95% CI: 0.73-0.95, p=0.005).

This pooled analysis of reported randomized trials did not reveal a statistically significant effect between adjuvant VEGFR-targeted therapy and improved DFS or OS in patients with intermediate/high-risk local or regional fully resected RCC. Improvement in DFS may be more likely with the use of full-dose regimens, pending further results. However, adjuvant treatment was associated with high-grade AEs.

Vascular endothelial growth factor receptor-targeted therapy after nephrectomy for localized kidney cancer is not associated with consistent improvements in delaying cancer recurrence or prolonging life and comes at the expense of potentially significant side effects.

European urology. 2018 May 18 [Epub ahead of print]

Maxine Sun, Lorenzo Marconi, Tim Eisen, Bernard Escudier, Rachel H Giles, Naomi B Haas, Lauren C Harshman, David I Quinn, James Larkin, Sumanta K Pal, Thomas Powles, Christopher W Ryan, Cora N Sternberg, Robert Uzzo, Toni K Choueiri, Axel Bex

Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Department of Urology, Coimbra University Hospital, Coimbra, Portugal., Department of Oncology, Addenbrooke's Hospital, Cambridge Biomedical Research Centre, UK., Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France., Patient Advocate, International Kidney Cancer Coalition, Duivendrecht, The Netherlands; Department Nephrology and Hypertension, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, University of Utrecht, The Netherlands., Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA., Section of Genitourinary Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA., Royal Marsden NHS Trust Foundation Trust, London, UK., Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA., The Royal Free NHS Trust and Barts Cancer Institute, Queen Mary University of London, London, UK., Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA., Department of Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy., Department of Surgery, Fox Chase Cancer Center - Temple University Health System, Philadelphia, PA, USA., Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: ., Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Electronic address: .

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