MP14-04 ADJUVANT THERAPY WITH TYROSINE KINASE INHIBITORS FOR RENAL CELL CARCINOMA: AN UPDATED SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I (MP14)1 Sep 2021MP14-04 ADJUVANT THERAPY WITH TYROSINE KINASE INHIBITORS FOR RENAL CELL CARCINOMA: AN UPDATED SYSTEMATIC REVIEW AND META-ANALYSIS Ekaterina Laukhtina, Fahad Quhal, Keiichiro Mori, Dmitry Enikeev, Pierre I. Karakiewicz, Manuela Schmidinger, and Shahrokh F. Shariat Ekaterina LaukhtinaEkaterina Laukhtina More articles by this author , Fahad QuhalFahad Quhal More articles by this author , Keiichiro MoriKeiichiro Mori More articles by this author , Dmitry EnikeevDmitry Enikeev More articles by this author , Pierre I. KarakiewiczPierre I. Karakiewicz More articles by this author , Manuela SchmidingerManuela Schmidinger More articles by this author , and Shahrokh F. ShariatShahrokh F. Shariat More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001995.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Tyrosine kinase inhibitors (TKIs) have been widely used in the management of patients with metastatic renal cell carcinoma (RCC). However, the use of systemic therapies in the adjuvant setting of localized and locally advanced RCC has shown conflicting results across the literature. Therefore, we aimed to conduct an updated systematic review and meta-analysis comparing the efficacy and safety of TKIs in the adjuvant setting for patients with localized and locally advanced RCC. METHODS: The MEDLINE and EMBASE databases were searched in December 2020 to identify phase III randomized controlled trials (RCT) of patients receiving adjuvant therapies with TKI for RCC. Disease-free survival (DFS) and overall survival (OS) were the primary endpoints. The secondary endpoints included treatment-related adverse events (TRAEs) of high and any grade. Forest plots were used to describe the relationships between treatment and survival outcomes as well as TRAEs (TKI therapy versus placebo). RESULTS: Five trials (S-TRAC, ASSURE, PROTECT, ATLAS, and SORCE) were included in our meta-analysis comprising 6,531 patients. The forest plot revealed that TKI therapy was associated with a significantly longer DFS compared to placebo (pooled HR:0.88, 95%CI: 0.81–0.96, p=0.004). The Cochrane’s Q test (p=0.51) and I2 test (I2=0%) revealed no significant heterogeneity. Adjuvant TKI was not associated with improved OS compared to placebo (pooled HR:0.93, 95%CI: 0.83–1.04, p=0.23). The Cochrane’s Q test (p=0.74) and I2 test (I2=0%) revealed no significant heterogeneity.The forest plot revealed that TKI therapy, compared to placebo, was associated with higher rates of high grade TRAEs (OR:5.20, 95%CI: 4.10–6.59, p<0.00001) as well as any grade TRAEs (OR:3.85, 95%CI: 1.22–12.17, p=0.02). The Cochrane’s Q tests (P<0.0001 and p<0.00001, respectively) and I2 tests (I2=79% and I2=90%, respectively) revealed significant heterogeneity. CONCLUSIONS: The findings of our analyses suggest an improved DFS in patients with localized and locally advanced RCC receiving adjuvant TKI as compared to placebo; however, this did not translate into any significant OS benefit. Additionally, TKI therapy led to significant toxicity. Adjuvant TKI does not seem to offer a satisfactory risk/ benefit balance for all patients. Select patients with very poor prognosis may be considered in a shared decision-making process with the patient. With the successful arrival of immune-based therapies in RCC, these may allow a more favorable risk/benefit profile. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e253-e253 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ekaterina Laukhtina More articles by this author Fahad Quhal More articles by this author Keiichiro Mori More articles by this author Dmitry Enikeev More articles by this author Pierre I. Karakiewicz More articles by this author Manuela Schmidinger More articles by this author Shahrokh F. Shariat More articles by this author Expand All Advertisement Loading ...