Association of the circulating lipid panel, PCPro, with clinical outcomes in metastatic hormone-sensitive prostate cancer: post hoc analysis of the ENZAMET phase III randomised trial (ANZUP 1304)

Lin, HM; Huynh, K; Scheinberg, T; Portman, N; Kim, RMN; Mellor, R; Faulkner, AN; Mellett, NA; Davis, ID; Martin, A; Sullivan, D; Joshua, A; McJannett, M; Subhash, V; Yip, S; Azad, AA; Marschner, IC; North, SA; McDermott, RS; Chi, KN; Stockler, MR; Sweeney, CJ; Meikle, PJ; Horvath, LG

Author(s): Lin, HM; Huynh, K; Scheinberg, T; Portman, N; Kim, RMN; Mellor, R; Faulkner, AN; Mellett, NA; Davis, ID; Martin, A; Sullivan, D; Joshua, A; McJannett, M; Subhash, V; Yip, S; Azad, AA; Marschner, IC; North, SA; McDermott, RS; Chi, KN; Stockler, MR; Sweeney, CJ; Meikle, PJ; Horvath, LG;
Details: Publication Year 2025-09,Volume 36,Issue #9,Page 1068-1077
Journal Title: Annals of Oncology
Publication Type: Research article
Abstract: BACKGROUND: Enzalutamide significantly improves overall survival (OS) of patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, ∼10% of patients will die within 2 years. PCPro is a plasma lipid panel associated with decreased OS in metastatic castration-resistant prostate cancer. In this study, we assessed the association between PCPro and clinical outcomes in mHSPC by carrying out a post hoc analysis of ENZAMET, the landmark phase III trial comparing enzalutamide with nonsteroidal anti-androgen (NSAA). PATIENTS AND METHODS: PCPro status was determined by liquid chromatography-mass spectrometry analysis of plasma samples from 866 participants (77% of the ENZAMET trial cohort), before treatment (n = 866) and at first progression (n = 282). Outcomes examined were OS and clinical progression-free survival (clinPFS). RESULTS: Participants with a positive PCPro status at baseline (13.4%) had a significantly shorter OS and clinPFS compared with those with a negative PCPro status [OS hazard ratio (HR) 1.81, 95% CI 1.40-2.33, clinPFS HR 1.65, 95% CI 1.32-2.07, P < 0.0001]. PCPro is an independent prognostic factor when modelled with key clinical prognostic factors (P < 0.001). Enzalutamide (compared with NSAA) improved the OS of PCPro-negative participants (HR 0.61, P < 0.0001), but not the survival of PCPro-positive participants (HR 1.10, P = 0.69; interaction P = 0.024). Participants who were PCPro positive at progression have a shorter OS than those who were negative, irrespective of baseline status (median OS 24-28 months versus 42-45 months). CONCLUSIONS: PCPro status is a prognostic biomarker and predictive of the lack of OS benefit from enzalutamide compared with NSAA in mHSPC. These findings provide a rationale for testing therapeutic agents that can modify circulating lipid profiles in mHSPC.
Publisher: Elsevier
Keywords: Humans; Male; Benzamides; *Phenylthiohydantoin/analogs & derivatives/therapeutic use; Nitriles; Aged; *Prostatic Neoplasms, Castration-Resistant/drug therapy/blood/mortality/pathology; Middle Aged; *Lipids/blood; *Biomarkers, Tumor/blood; Progression-Free Survival; Prognosis; ceramide; enzalutamide; lipid biomarker; metastatic hormone-sensitive prostate cancer; therapeutic resistance
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1016/j.annonc.2025.05.529
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Creation Date: 2025-06-03 07:20:27

Last Modified: 2025-09-09 04:09:12