PD61-11 A PHASE II STUDY OF 6-MONTHS APALUTAMIDE PRIOR TO RADICAL PROSTATECTOMY IN INTERMEDIATE RISK PATIENTS TO REDUCE THE FREQUENCY OF PATHOLOGIC FEATURES THAT DRIVE POST-OPERATIVE RADIATION THERAPY

摘要

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy V (PD61)1 Sep 2021PD61-11 A PHASE II STUDY OF 6-MONTHS APALUTAMIDE PRIOR TO RADICAL PROSTATECTOMY IN INTERMEDIATE RISK PATIENTS TO REDUCE THE FREQUENCY OF PATHOLOGIC FEATURES THAT DRIVE POST-OPERATIVE RADIATION THERAPY John Davis, Brian Chapin, Curtis Pettaway, Lisly Chery, Louis Pisters, John Ward, John Papadopoulos, Ashish Kamat, Marisa Lozano, Patricia Troncoso, and Christopher Logothetis John DavisJohn Davis , Brian ChapinBrian Chapin , Curtis PettawayCurtis Pettaway , Lisly CheryLisly Chery , Louis PistersLouis Pisters , John WardJohn Ward , John PapadopoulosJohn Papadopoulos , Ashish KamatAshish Kamat , Marisa LozanoMarisa Lozano , Patricia TroncosoPatricia Troncoso , and Christopher LogothetisChristopher Logothetis View All Author Informationhttps://doi.org/10.1097/JU.0000000000002098.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Combination surgery followed by radiation is often required to effectively treat intermediate risk localized prostate cancer. In unfavorable intermediate risk treated by radical prostatectomy, histopathology will show approximately 50% with at least one adverse feature, and approximately 35% will drive post-operative radiation therapy--pT3a/b and/or positive surgical margins (PSM). This study was designed to explore the hypothesis that 6-months neoadjuvant apalutamide monotherapy (a potent nonsteroidal antiandrogen) prior to radical prostatectomy would reduce such risk, with minimal short-term side effects. The overall goal of the study was to reduce the the need for post-operative radiation without compromising efficacy. METHODS: This was a single center, phase II, open label, therapeutic evaluation trial of 6-months neoadjuvant apalutamide, followed by robot-assisted radical prostatectomy and extended pelvic lymphadenectomy. Eligible patients had unfavorable intermediate risk disease and selected for prostatectomy with extended pelvic node dissection. The primary aim was to determine if the study patients would have an aggregate 15% rate of high-risk surgical pathology (pT3a/b and/or PSM) compared to an expected 35% from historical controls. Secondary aims included safety/tolerability, quality of life, biochemical failure, and planned exploratory biomarker studies. RESULTS: The study was completed from May, 2018-February 2020 with a planned accrual of 43 patients completing study and surgery. The drug was tolerated well with one patient discontinuing early for a grade 3 rash. All patients had a >50% decline in PSA and expected elevations in testosterone while on drug, with normalization after discontinuation to a mean of 408 ng/dL. For the primary aim: 18 (42%) of 43 completing surgery had high risk surgical pathology. Other pathologic observations included 9.3% PSM (0 in pT2, 4 in pT3a/b). All PSM were focal. Only 1 patient (2%) of 43 had a positive node with an extended template. As of 2/2021, 93% are disease-free with median 13 months follow-up. There was one postoperative death unrelated (cardiac), 1 BCR with no treatment (pT2 disease), and 2 BCR leading to salvage RT (pT3a/b disease). CONCLUSIONS: A strategy of a pre-operative anti-androgen (non-castrating) neoadjuvant therapy prior to radical prostatectomy did not achieve the primary endpoint of reducing the expected frequency of adverse pathology. The study drug was well tolerated and showed proof-of-principle that intermediate risk patients can be enrolled to novel drug neoadjuvant surgical trials. The rates of positive margins and lymph node disease were lower than expected. Further follow-up is needed to determine any actual reduction in postoperative radiation, and provide further insight into whether pathologic findings are effective surrogate markers in the neoadjuvant treatment paradigm. Source of Funding: Janssen Pharmaceuticals © 2021 by Ame