Abstract 634P
Background
The addition of docetaxel to androgen-deprivation therapy (ADT) is associated with survival benefit in patients with hormone-naive metastatic prostate cancer (PCa), but was not found to be beneficial in high-risk patients presenting with rising PSA after primary local therapy (Oudard S et al, JAMA Oncol 2019). The objective was to assess the decline kinetics of PSA using mathematical modeling, and investigate the prognostic/predictive value of kinetic parameters.
Methods
The dataset of the randomized phase III trial comparing ADT with/without docetaxel on PSA-progression free survival (PFS) in 252 patients with a rising PSA levels after primary local therapy and with high-risk of recurrence was investigated. The PSA longitudinal kinetics during treatment was assessed using a Kinetic-Pharmacodynamic (K-PD) model (same as developed for CA-125 in You B et al, CCR 2020). Individual values of the modeled ELIMination rate constant parameter (KELIM) were calculated, and used to categorize patients with favorable or unfavorable KELIM (< or ≥ median) and further correlated with PFS/OS.
Results
Of the 252 patients, 177 patients were assessable for KELIM calculation. The median KELIM was 0.0873. Median follow-up was 9.8 years. Using univariate analyses, KELIM exhibited significant prognostic value regarding patient survival (median PSA-PFS, 10.1 vs 15.1 months, P < 0.001; median OS, 157 vs NA months, P = 0.041). The prognostic value of KELIM was significant against other prognostic factors using multivariate analyses for PSA-PFS (HR = 0.65, 95% CI 0.44-0.95, P = 0.026), and OS (HR = 0.55, 95% CI 0.33-0.91, P = 0.021), in addition to primary therapy type (surgery vs radiation therapy) (PSA-PFS) & PSA doubling-time prior to study entry (OS). The prognostic value of KELIM was stronger than ≥ 50% PSA response. KELIM prognostic value did not depend on treament arm.
Conclusions
This is the first study assessing the prognostic value of KELIM applied to PSA in rising PSA PCa patients. PSA KELIM was found to exhibit strong and independent prognostic value regarding PSA-PFS and OS in patients treated with ADT +/- docetaxel.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
UCBL.
Funding
Institut de Recherche sur les Cancers et le Sang (IRCS).
Disclosure
B. You: Financial Interests, Personal, Other, Consulting: AZ; Financial Interests, Personal, Other, Consulting: Roche; Financial Interests, Personal, Other, Consulting: GSK; Financial Interests, Personal, Other, Consulting: MSD; Financial Interests, Personal, Other, Consulting: Novartis; Financial Interests, Personal, Other, Consulting: ECS Progastrin; Financial Interests, Personal, Other, Consulting: Amgen; Financial Interests, Personal, Other, Consulting: Clovis; Financial Interests, Personal, Other, Consulting: Merck Serono. S. Oudard: Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Jassen; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Sanofi. All other authors have declared no conflicts of interest.