Abstract 1422P
Background
In a previous exploratory study, the modeled longitudinal PSA kinetics during the first 100 days of endocrine therapy +/- docetaxel was associated with progression-free survival (PFS) and overall survival (OS) (Carrot et al, Cancers 2022). The prognostic value of the early modeled PSA kinetics had to be confirmed. The objective was to assess the PSA decline kinetics using mathematical modelling, and investigate the prognostic/predictive value of kinetic parameters in FIRSTANA trial.
Methods
The randomized trial FIRSTANA (NCT01308567) comparing cabazitaxel and docetaxel on PFS and OS in mCRPC patients dataset was investigated. The PSA longitudinal kinetics during the treatment was assessed using the previous Kinetic-Pharmacodynamic (K-PD) model. Individual values of the modeled ELIMination rate constant (KELIM) and PRODuction rate (KPROD) parameters were calculated, and used to categorize patients with favorable or unfavorable KELIM and KPROD (< or ≥ median) and further correlated with PFS/OS.
Results
Of the 1168 patients, 1050 patients were assessable for KELIM and KPROD calculation. Median KELIM was 0.02 (days-1) and median KPROD 0.2 (ng.mL-1.days-1). Median follow-up was 22.6 months. Using univariate analyses, KELIM exhibited significant prognostic value regarding patient survival (median PFS, 3.6 vs 4.7 months, P = 0.002; median OS, 17.4 vs 28.4 months, P < 0.001), as did KPROD (median PFS, 3.4 vs 4.9 months, P < 0.001; median OS, 17.1 vs 31.3 months, P < 0.001). In multivariate analyses, KELIM & KPROD were significant for PFS (KELIM, HR = 0.79, 95% CI 0.67-0.93; KPROD, HR = 0.73, 95% CI 0.62-0.86), and for OS (KELIM, HR = 0.51, 95% CI 0.44-0.60; KPROD, HR = 0.42, 95% CI 0.35-0.50), together with baseline tumor progression and PSA doubling-time prior to study entry.
Conclusions
This external validation study confirmed the results previously reported about the prognostic value of the early PSA longitudinal kinetics, assessed by KELIM and KPROD, regarding PFS and OS in mCRPC patients treated with taxanes. They could be used to stratify patients based on their prognosis, as a way of adjusting the disease management.
Clinical trial identification
NCT01308567.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Oudard: Financial Interests, Personal, Advisory Board, Consultancy, Advisory Role: Sanofi; Financial Interests, Personal, Invited Speaker, Public Speaking and Advisory Role: Janssen; Financial Interests, Personal, Advisory Board, Advisory Role and Public Speaking: AstraZeneca, MSD, Merck, Astellas, Ipsen, Pfizer, Roche, Genentech; Financial Interests, Personal, Advisory Board, Advirory Board and Public Speaking: BMS, Bayer, Novartis. K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas, Bayer, Janssen, AAA, MSD, AstraZeneca, Novartis/AAA, Pfizer; Financial Interests, Institutional, Invited Speaker: Astellas, Bayer, Janssen, Sanofi, MSD, AstraZeneca, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Curevac, Orion; Financial Interests, Institutional, Research Grant, Trial Chair: Pfizer, Bayer, AstraZeneca, Orion, MSD, BMS, Janssen; Non-Financial Interests, Principal Investigator, Chair of the 7DX phase 3 trial: BMS; Non-Financial Interests, Principal Investigator, Chair of the Docetaxel-pembrolizumab phase 3 trial: Merck; Non-Financial Interests, Principal Investigator, Chair of the Darolutamide BCR phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the PSMAfore phase 3 trial: AAA/Novartis; Non-Financial Interests, Principal Investigator, Chair of the CYPIDES ODM-208 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the STESIDES ODM-209 Phase I-II trial: Orion. All other authors have declared no conflicts of interest.