MP24-08 RELATIONSHIPS OF SITES AND BURDEN OF METASTASES WITH LONG-TERM OUTCOMES AND MOLECULAR SUBTYPES IN TITAN

Abstract

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) II (MP24)1 Sep 2021MP24-08 RELATIONSHIPS OF SITES AND BURDEN OF METASTASES WITH LONG-TERM OUTCOMES AND MOLECULAR SUBTYPES IN TITAN Anders Bjartell, Neeraj Agarwal, Lawrence Karsh, Axel S. Merseburger, Andrea J. Pereira de Santana Gomes, Álvaro Juárez Soto, Robert Given, Amitabha Bhaumik, Sabine Brookman-May, Florence Lefresne, Suneel D. Mundle, Sharon A. McCarthy, Shibu Thomas, Justin Lucas, Clemente Aguilar-Bonavides, Hirotsugu Uemura, Simon Chowdhury, and Kim N. Chi Anders BjartellAnders Bjartell More articles by this author , Neeraj AgarwalNeeraj Agarwal More articles by this author , Lawrence KarshLawrence Karsh More articles by this author , Axel S. MerseburgerAxel S. Merseburger More articles by this author , Andrea J. Pereira de Santana GomesAndrea J. Pereira de Santana Gomes More articles by this author , Álvaro Juárez SotoÁlvaro Juárez Soto More articles by this author , Robert GivenRobert Given More articles by this author , Amitabha BhaumikAmitabha Bhaumik More articles by this author , Sabine Brookman-MaySabine Brookman-May More articles by this author , Florence LefresneFlorence Lefresne More articles by this author , Suneel D. MundleSuneel D. Mundle More articles by this author , Sharon A. McCarthySharon A. McCarthy More articles by this author , Shibu ThomasShibu Thomas More articles by this author , Justin LucasJustin Lucas More articles by this author , Clemente Aguilar-BonavidesClemente Aguilar-Bonavides More articles by this author , Hirotsugu UemuraHirotsugu Uemura More articles by this author , Simon ChowdhurySimon Chowdhury More articles by this author , and Kim N. ChiKim N. Chi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002015.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The final analysis of TITAN confirmed improvement in long-term outcomes in metastatic castration-sensitive prostate cancer (mCSPC) with apalutamide (APA) + androgen deprivation therapy (ADT) (Chi ASCO GU 2021). We assessed relationships between the number and location of metastases, signatures associated with poor prognosis and ADT insensitivity and outcome measures. METHODS: 1052 mCSPC pts with ≥1 bone lesion were randomized 1:1 to APA (240 mg QD) or placebo (PBO)+ADT, and were stratified by sites of metastases. Outcomes in APA-treated pts (n=525) (Table) were analyzed by Kaplan-Meier and Cox proportional hazards methods. Molecular subtypes from 222 primary tumors (biomarker population; APA=110, PBO=112) were defined using biologically distinct signatures categorized by expression levels: androgen receptor activity (AR-A) high to average vs low, genomic classifier (GC) score high vs low to average, basal vs luminal (A + B), hypoxia high vs low, and adenocarcinoma vs neuroendocrine-like small-cell 3 score. The association between categorical expression and sites of metastases was assessed with Fisher’s exact test. RESULTS: In 1052 TITAN pts, metastases at baseline (BL) were: 53.0% in bone only, 37.9% in bone +1 other location, 9.0% in bone +2 or 3 other locations; 38.3% of pts had >10 bone lesions. The risk of worse outcomes in APA-treated pts increased with an increased number of metastatic locations and with >10 bone lesions (Table). Multiple metastatic locations at BL were significantly associated with higher risk of worse outcomes vs bone-only metastases (Table 1). In the biomarker population, 43.2% had AR-A low, 74.8% GC high, 50.5% basal, 50.0% hypoxia low, and 83.8% adenocarcinoma subtypes. Primary tumors from pts with i) bone-only metastases or ii) concomitant bone and visceral metastases were significantly enriched for low levels of hypoxia or adenocarcinoma (i), or for basal, AR-A low, or neuroendocrine-like features, respectively (ii) (p<0.05 for all). CONCLUSIONS: In APA-treated TITAN pts, multiple anatomic locations and >10 bone metastases were significantly associated with worse oncologic outcomes in mCSPC. Association of poor-prognosis and ADT-insensitivity signatures with metastatic locations needs further investigation. Source of Funding: Janssen Research & Development © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e414-e415 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anders Bjartell More articles by this author Neeraj Agarwal More articles by this author Lawrence Karsh More articles by this author Axel S. Merseburger More articles by this author Andrea J. Pereira de Santana Gomes More articles by this author Álvaro Juárez Soto More articles by this author Robert Given More articles by this author Amitabha Bhaumik More articles by this author Sabine Brookman-May More articles by this author Florence Lefresne More articles by this author Suneel D. Mundle More articles by this author Sharon A. McCarthy More articles by this author Shibu Thomas More articles by this author Justin Lucas More articles by this author Clemente Aguilar-Bonavides More articles by this author Hirotsugu Uemura More articles by this author Simon Chowdhury More articles by this author Kim N. Chi More articles by this author Expand All Advertisement Loading ...