LBA02-05 NAXIVA - A PHASE II NEOADJUVANT STUDY OF AXITINIB FOR REDUCING EXTENT OF VENOUS TUMOR THROMBUS IN CLEAR CELL RENAL CELL CANCER WITH VENOUS INVASION: TRANSLATIONAL RESULTS

Abstract

You have accessJournal of UrologyLate-breaking Abstract II - Malignant1 Sep 2021LBA02-05 NAXIVA - A PHASE II NEOADJUVANT STUDY OF AXITINIB FOR REDUCING EXTENT OF VENOUS TUMOR THROMBUS IN CLEAR CELL RENAL CELL CANCER WITH VENOUS INVASION: TRANSLATIONAL RESULTS Sarah J Welsh, James Jones, Stephan Ursprung, Christopher Smith, Ferdia Gallagher, and Grant Stewart Sarah J WelshSarah J Welsh More articles by this author , James JonesJames Jones More articles by this author , Stephan UrsprungStephan Ursprung More articles by this author , Christopher SmithChristopher Smith More articles by this author , Ferdia GallagherFerdia Gallagher More articles by this author , and Grant StewartGrant Stewart More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002149.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Venous tumor thrombus (VTT) extension occurs in 4-15% cases of renal cell cancer (RCC). Although surgery is performed with curative intent, mortality is high (5-15%). The NAXIVA trial provided the first level II evidence in this patient group, assessing the response of VTT to axitinib (TKI). The primary endpoint of percentage of evaluable patients with an improvement in VTT according to the Mayo classification was positive at 26.58%. 35.29% had a change in surgical approach to a less invasive option. Median % reduction in VTT height was 21.49%. Response rate (RECIST) was 61.90% SD, 14.29% PR, 9.52% PD. We now present the results of translational studies examining the role of the tumor microenvironment (TME) and response to axitinib. METHODS: NAXIVA was a single arm, single agent, multi-center, phase 2 feasibility study of 8 weeks axitinib in RCC patients with clear cell RCC prior to nephrectomy/thrombectomy. 21 patients were recruited (15/Dec/2017-06/Jan/2020) at 5 UK sites. Extensive translational sampling (tissue, blood, urine) was performed before starting axitinib, during treatment and at nephrectomy. Samples were processed and analysed for ctDNA (shallow whole genome sequencing), TME (multiparameter immunofluorescence, flow cytometry), and cytokines (multiplex assays). RESULTS: Consistent with previous studies showing low detection of ctDNA in RCC, only 3/21 patients had detectable ctDNA at baseline (2 in plasma, 1 in urine); there was no concordance in the levels or composition of ctDNA between the plasma and urine. No patients with detectable ctDNA at baseline showed a RECIST response or had a change in surgical approach to axitinib. Consistent with its mechanism of action, axitinib treatment reduced vessel density (CD34+ and CD31+CD34+) in all patients. There was a trend towards responders showing higher baseline vessel density and area, with a greater reduction after 8 weeks treatment than non-responders. Interestingly, responders also demonstrated lower CD8+PD1+ tumor infiltration consistent with previous data suggesting such patients may respond better to TKIs than immunotherapy. No individual cytokine or peripheral immune cell-based biomarkers have predicted response but multiparameter analysis is on-going. CONCLUSIONS: NAXIVA has provided unique prospective data on neoadjuvant axitinib to down stage IVC VTT and reduce extent of surgery. Translational work has identified potential biomarkers for validation in future studies, with work on-going. Source of Funding: Educational grant from Pfizer © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1177-e1177 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sarah J Welsh More articles by this author James Jones More articles by this author Stephan Ursprung More articles by this author Christopher Smith More articles by this author Ferdia Gallagher More articles by this author Grant Stewart More articles by this author Expand All Advertisement Loading ...