Association of the circulating lipid panel, PCPro, with clinical outcomes in metastatic hormone-sensitive prostate cancer: post-hoc analysis of the ENZAMET Phase 3 randomised trial (ANZUP 1304)
- Author(s)
- Lin, HM; Scheinberg, T; Portman, N; Kim, RMN; Mellor, R; Hunyh, K; 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;
- Journal Title
- Annals of Oncology
- Publication Type
- Online publication before print
- 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 performing a post-hoc analysis of ENZAMET, the landmark phase 3 trial comparing enzalutamide to non-steroidal anti-androgen (NSAA). PATIENTS AND METHODS: PCPro status was determined by liquid chromatography-mass spectrometry analysis of plasma samples from 866 participants (77% of 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 significantly shorter OS and clinPFS compared to those with a negative PCPro status (OS HR=1.81; clinPFS HR=1.65; p<0.0001). PCPro is an independent prognostic factor when modelled with key clinical prognostic factors (p<0.001). Enzalutamide (compared to 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 shorter OS than those who were negative, irrespective of baseline status (median OS 24-28 months versus 42-45 months). CONCLUSION: PCPro status is a prognostic biomarker and predictive of the lack of OS benefit from enzalutamide compared to NSAA in mHSPC. These findings provide a rationale for testing therapeutic agents that can modify circulating lipid profiles in mHSPC.
- Keywords
- Metastatic hormone-sensitive prostate cancer; ceramide; enzalutamide; lipid biomarker; therapeutic resistance
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1016/j.annonc.2025.05.529
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-06-03 07:20:27
Last Modified: 2025-06-03 07:20:41