PD52-03 A MULTICENTER PHASE 1B/2 STUDY OF NEOADJUVANT PEMBROLIZUMAB AND CISPLATIN CHEMOTHERAPY FOR MUSCLE INVASIVE UROTHELIAL CANCER

You have accessJournal of UrologyBladder Cancer: Invasive V (PD52)1 Apr 2019PD52-03 A MULTICENTER PHASE 1B/2 STUDY OF NEOADJUVANT PEMBROLIZUMAB AND CISPLATIN CHEMOTHERAPY FOR MUSCLE INVASIVE UROTHELIAL CANCER Hristos Kaimakliotis*, Costantine Albany, Jean Hoffman-Censits, Edouard Trabulsi, W. Kevin Kelly, Joel Picus, Nabil Adra, Clint Cary, Michael Koch, Mark Fleming, Radhika Walling, J. Luke Godwin, Robert Abouassaly, Matthew Cooney, Pingfu Fu, Ariel Nelson, Ginu Xavier, Lee Ponsky, and Christopher Hoimes Hristos Kaimakliotis*Hristos Kaimakliotis* , Costantine AlbanyCostantine Albany , Jean Hoffman-CensitsJean Hoffman-Censits , Edouard TrabulsiEdouard Trabulsi , W. Kevin KellyW. Kevin Kelly , Joel PicusJoel Picus , Nabil AdraNabil Adra , Clint CaryClint Cary , Michael KochMichael Koch , Mark FlemingMark Fleming , Radhika WallingRadhika Walling , J. Luke GodwinJ. Luke Godwin , Robert AbouassalyRobert Abouassaly , Matthew CooneyMatthew Cooney , Pingfu FuPingfu Fu , Ariel NelsonAriel Nelson , Ginu XavierGinu Xavier , Lee PonskyLee Ponsky , and Christopher HoimesChristopher Hoimes View All Author Informationhttps://doi.org/10.1097/01.JU.0000556959.45525.89AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: We sought to assess if pembrolizumab (pembro) improves the pathologic response rate in locally advanced urothelial carcinoma (UC) when combined with gemcitabine (G) and cisplatin (C) neoadjuvant chemotherapy (NAC) through a multicenter phase 1b/2 chemo-immunomodulation trial. Historically, the best pathologic non-muscle invasive rate (PaIR, ≤pT1N0M0) has been noted for neoadjuvant dose dense MVAC at ∼44%. METHODS: Cisplatin eligible patients with cT2-4aN0M0 UC were treated with pembro 200mg q3wks on day 8 for 5 doses; with C (70mg/m2) day 1, and G (1000mg/m2) days 1 and 8 of a 21-day cycle, for 4 cycles; followed by radical cystectomy (RC). Minimum criteria for evaluation of safety was one dose pembro and for efficacy two doses and RC. The primary endpoint was PaIR of ≥48%, and secondary endpoints included safety and tolerability, RC rate, relapse free-, disease specific-, and overall survival. RESULTS: Forty patients (pts) were accrued: median age was 65 years, 75% were male, 10% had mixed UC histology, and PD-L1 combined positive score ≥10 was 52%. No dose-limiting toxicities were noted in the 6 pts on phase 1b. Average number of doses given (vs intended) for pembro=4.3(5), C=3.7(4), G=7.2(8). There was 1 death on post-RC day 9 due to mesenteric ischemia. One pt did not have RC due to adverse event (AE), gr4 thrombocytopenic purpura; UC in remission at 14mo, and 3 patients refused RC. One pt with presumed gr3 MI during cycle 4 had a negative cardiac workup and completed therapy and RC without further AE. One gr4 hyponatremia and ten gr3 events did not preclude RC (2-each thromboembolism, elevated creatinine, hyponatremia;1-each: dehydration, emesis, neutropenic fever, infection). Gr 3/4 cytopenias occurred in 57% of pts. Of 36 pts who had RC the median time to surgery was 5.3 wks from last dose. Baseline stage was cT2 51%, cT3 44%, cT4a 5%. The PaIR was 61%. Sixteen pts were downstaged to pT0 (44.4%), 3 to pTis (8.3%), and 3 to pT1 (8.3%). PaIR did not correlate with baseline PD-L1 score. At 17.4 (1.6-33.3) months median follow up, the relapse free-, overall-, and disease specific-survival, was 70%, 81%, and 90%, respectively. CONCLUSIONS: Neoadjuvant chemo-immunotherapy with pembro in locally advanced UC has manageable toxicity, a comparable time to surgery as NAC, and has improved pathologic outcomes compared to historic controls. Furthermore, the long-term effects of immunotherapy with a sustained high disease specific survival may provide control rates that warrant further study. Clinical trial identification Clinicaltrials.gov: NCT02365766 Source of Funding: Hoosier Cancer Research Network Indianapolis, IN; Philadelphia, PA; St. Louis, MO; Indianapolis, IN; Norfolk, VA; Indianapolis, IN; Kenilworth, NJ; Cleveland, OH; Indianapolis, IN; Cleveland, OH© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e924-e925 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hristos Kaimakliotis* More articles by this author Costantine Albany More articles by this author Jean Hoffman-Censits More articles by this author Edouard Trabulsi More articles by this author W. Kevin Kelly More articles by this author Joel Picus More articles by this author Nabil Adra More articles by this author Clint Cary More articles by this author Michael Koch More articles by this author Mark Fleming More articles by this author Radhika Walling More articles by this author J. Luke Godwin More articles by this author Robert Abouassaly More articles by this author Matthew Cooney More articles by this author Pingfu Fu More articles by this author Ariel Nelson More articles by this author Ginu Xavier More articles by this author Lee Ponsky More articles by this author Christopher Hoimes More articles by this author Expand All Advertisement PDF downloadLoading ...