MP14-05 ADJUVANT VEGF-TKI INHIBITORS AFTER SURGERY IMPROVES PROGRESSION FREE SURVIVAL (BUT NOT SURVIVAL) IN HIGH-RISK RCC PATIENTS

Abstract

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I (MP14)1 Sep 2021MP14-05 ADJUVANT VEGF-TKI INHIBITORS AFTER SURGERY IMPROVES PROGRESSION FREE SURVIVAL (BUT NOT SURVIVAL) IN HIGH-RISK RCC PATIENTS Giuseppe Fallara, Marco Bandini, Alessandro Larcher, Giuseppe Rosiello, Alberto Martini, Giuseppe Basile, Gianmarco Colandrea, Daniele Cignoli, Pierre Karakiewicz, Zhe Tian, Federico Pederzoli, Andrea Necchi, Andrea Salonia, Alberto Briganti, Roberto Bertini, Francesco Montorsi, Axel Bex, and Umberto Capitanio Giuseppe FallaraGiuseppe Fallara More articles by this author , Marco BandiniMarco Bandini More articles by this author , Alessandro LarcherAlessandro Larcher More articles by this author , Giuseppe RosielloGiuseppe Rosiello More articles by this author , Alberto MartiniAlberto Martini More articles by this author , Giuseppe BasileGiuseppe Basile More articles by this author , Gianmarco ColandreaGianmarco Colandrea More articles by this author , Daniele CignoliDaniele Cignoli More articles by this author , Pierre KarakiewiczPierre Karakiewicz More articles by this author , Zhe TianZhe Tian More articles by this author , Federico PederzoliFederico Pederzoli More articles by this author , Andrea NecchiAndrea Necchi More articles by this author , Andrea SaloniaAndrea Salonia More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Roberto BertiniRoberto Bertini More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Axel BexAxel Bex More articles by this author , and Umberto CapitanioUmberto Capitanio More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001995.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The use of adjuvant vascular endothelial growth factor–tyrosine kinase inhibitor (VEGF-TKI) agents after curative intent nephrectomy for renal cell carcinoma (RCC) are still matter of debate. The ASSURE, PROTECT and ATLAS trial failed to meet their primary end-points. Conversely, S-TRAC showed a disease-free survival (DFS) benefit. Recently, the SORCE trial was published. We aimed to re-assess the role of VEGF-TKIs after the publication of this last trial. METHODS: A systematic meta-analysis including 5 published RCTs was performed based on the PRISMA guidelines. DFS, overall survival (OS) and risk of adverse events of grade >3 as for Common Terminology Criteria for Adverse Events (CTCAE) classification were assessed in both arms. Sub analysis were conducted for high-risk patients and for clear cell RCC. Different definitions of high-risk subgroups were used: for the ATLAS, ASSURE and S-TRAC trials high- risk patients were defined as those with at least pT3 and/or pN1 diseases, for the SORCE trial high-risk patients were defined as those with Leibovich score 6-11, whereas for the PROTECT trial no sub analysis for high-risk patients was available. Hazard ratios (HR) and relative risk (RR) were pooled and tested using Z scores, with the significance level set at p<0.05. I2 statistic and Tau2 were used to assess heterogeneity across the studies. RESULTS: We found a marginal positive HR of 0.92 (95% confidence interval [CI] 0.85-1.00; p-value=0.049) for DFS in favor of adjuvant VEGF-TKI agents. This benefit was more pronounced for DFS in the sub-groups of only high-risk patients (HR: 0.89, 95% CI 0.80-0.99; p-value=0.026), but less pronounced in ccRCC only subgroup (HR 0.92, 95% CI: 0.85-1.00; p-value=0.044). Overall survival benefit was instead not reached. However, pooled relative risk for high-grade (grade ≥3 according to CTCAE classification) adverse events was irremediably high, 2.56 (95% CI: 2.15-3.04; p- value<0.001). CONCLUSIONS: After SORCE trial, we provided level 1a evidence of beneficial effect of adjuvant therapy on DFS. However, given the marginal benefit in terms of DFS and the drawback of high-grade adverse events, adjuvant VEGF-TKIs therapy should not be recommended in non-metastatic high-risk RCC after surgery, even after the SORCE trial publication. Source of Funding: © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e253-e254 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Giuseppe Fallara More articles by this author Marco Bandini More articles by this author Alessandro Larcher More articles by this author Giuseppe Rosiello More articles by this author Alberto Martini More articles by this author Giuseppe Basile More articles by this author Gianmarco Colandrea More articles by this author Daniele Cignoli More articles by this author Pierre Karakiewicz More articles by this author Zhe Tian More articles by this author Federico Pederzoli More articles by this author Andrea Necchi More articles by this author Andrea Salonia More articles by this author Alberto Briganti More articles by this author Roberto Bertini More articles by this author Francesco Montorsi More articles by this author Axel Bex More articles by this author Umberto Capitanio More articles by this author Expand All Advertisement Loading ...