ASCO GU 2022: Treatment Outcomes for mCRPC Following Progression on Upfront ADT with Androgen Receptor Pathway Inhibitors for mCSPC

( The 2022 GU ASCO Annual meeting included a prostate cancer session highlighting work from Dr. Daniel Khalaf and colleagues presenting their results of treatment outcomes for mCRPC following progression on upfront ADT with androgen receptor pathway inhibitors (ARPIs) for mCSPC. Combined ADT and ARPI are associated with improved radiographic progression free survival (rPFS) and overall survival (OS) compared with ADT alone in patients with mCSPC. However, the activity of subsequent therapies such as docetaxel, radium-223, or a second ARPI at the time of progression to mCRPC is not well characterized.

This was a retrospective analysis of patients enrolled on a biobank at 6 cancer centers in British Columbia, Canada. Patients who received abiraterone or apalutamide for mCSPC were included, and data including baseline clinical prognostic factors and clinical outcomes (per Prostate Cancer Working Group III) were collected from patient records. Survival was analyzed by Kaplan-Meier method and Log Rank test and prognostic variables were determined using Cox regression.

There were 168 patients identified of which 126 (75%) received abiraterone, 38 (23%) received apalutamide, and 4 (2%) received one ARPI and switched to the other for toxicity. Median age was 69 years and Gleason score ≥ 8 in 61%. Site of metastasis at mCSPC was lymph node (n=91), bone (n=141), and liver (n=6). As of August 28, 2021, a total of 46 patients (27%) progressed to mCRPC, of which 38 (23%) received subsequent systemic therapy. First-line mCRPC treatments were docetaxel (n = 12, 32%), Radium-223 (n = 10, 26%), enzalutamide (n = 6, 16%), platinum chemotherapy (n = 3, 8%), and others (n = 7, 18%), including immune checkpoint inhibitors (n = 1) and Lutetium177-PSMA-617 (n = 1) and other investigational agents (n = 5). Outcomes for these patients, stratified by first-line mCRPC therapy is summarized as follows:

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The median OS from the onset of first-line mCRPC therapy was 9.7 months (95% CI 4.6-14.8):

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On univariate Cox analysis, clinical factors at time of mCRPC associated with worse OS were: LDH above upper limit of normal (HR 5.0, 95% CI 1.7-14.5), hemoglobin below lower limit of normal (HR 5.2, 95% CI 1.1-23.8), presence of ≥ 20 bone metastasis (HR 3.7, 95% CI 1.4-9.8), and increasing PSA (HR 1.002, 95% CI 1.001-1.003). On multivariable analysis, only LDH above upper limit of normal (HR 4.0, 95% CI 1.2-13.1) remained associated with worse OS.

Dr. Khalaf concluded his presentation assessing treatment outcomes for mCRPC following progression on upfront ADT with ARPIs for mCSPC with the following take-home messages:

  • PSA decline rates and survival are modest for patients who have progressed following upfront abiraterone or apalutamide plus ADT for mCSPC
  • Elevated LDH was an independent prognostic factor for overall survival in this setting
  • Further follow-up is required to accurately determine outcomes with current mCRPC standard therapies following up-front ADT + ARPI
  • Recently approved treatment options such as Lutetium177-PSMA-617 and PARP inhibitors for DNA damage repair deficient tumors may help to improve outcomes for these patients

Presented by: Daniel J. Khalaf, BC Cancer, Vancouver, Vancouver, BC, Canada, University of British Columbia, Vancouver, BC, Canada

Co-Authors: Liheng Chen, Katherine Sunderland, Joanna Vergidis, Krista Noonan, Daygen L. Finch, Muhammad Zulfiqar, Kim N. Chi

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022