AUA 2018: Systematic Review and Meta-Analysis of Adjuvant Therapy After Nephrectomy for High-risk, Non-metastatic Renal Cell Carcinoma

San Francisco, CA USA ( The current treatment for non-metastatic renal cell carcinoma (nmRCC) is either a partial or radical nephrectomy. However, many adjuvant therapies have been examined such as radiotherapy, vaccines, immunotherapy, Vascular Endothelial Growth Factor (VEGF)-TKI, and checkpoint inhibitors. Five trials, ASSURE, S-TRAC, PROTECT, SORCE, ATLAS, have been designed to evaluate the effect of adjuvant VEGF-based therapy in patients with nmRCC, who underwent either partial or radical nephrectomy. The ASSURE, S-TRAC and the PROTECT trials published their results.

Data was collected for 4,096 patients from the Embase, Medline, and Cochrane databases up to September 2017, with majority being extracted from the ASSURE and PRTOECT trial (47% and 38%, respectively). A meta-analysis combining the ASSURE, S-TRAC and PROTECT trials addressing disease-free survival (DFS) and overall survival (OS) was performed. Risk of bias and confounding assessments were performed.

ASSURE showed no DFS (p=0.7) or OS (p=0.66) benefit over placebo when compared to one year of sorafenib or sunitinib. However, central review data for the S-TRAC study showed improved DFS (p=0.03), but not with investigator review. There was no OS benefit for either study. The PROTECT trial also showed no DFS (p=0.16) or OS (p=0.16) benefit, when comparing pazopanib 600mg to placebo. However, when using pazopanib 800mg, improved DFS (p=0.02) was observed, but no record of OS (0.66) benefit. Within the meta-analysis, the pooled DFS and OS estimates from ASSURE, S-TRAC and PROTECT, resulted in respective DFS and OS hazard ratios of 0.92 (95%CI: 0.82-1.03) and 0.99 (95%CI: 0.85-1.17), when pazopanib 600mg was considered. Similarly, when pazopanib 800mg was considered, pooled DFS and OS hazard ratios were 0.87 (95%CI: 0.73-1.04) and 1.04 (95%CI: 0.89-1.22).

Until now adjuvant therapy for nmRCC shows no OS benefit and equivocal DFS benefit. Therefore, the study’s outcome suggests that the use of VEGF-inhibitors is not supported in clinical practice. One member of the audience raised a question about the comparison of these drugs given that they are used in different settings among different patient populations. Perhaps, further subgroup analyses will better determine or reconfirm the results of this study.

Presented by: Ariane Smith, MD

Written by: Rita Derderian, Department of Urology, University of California-Irvine at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA
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