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).

However, ∼10% of patients will die within 2 years.

然而，约有10%的患者在2年内会死亡。

PCPro is a plasma lipid panel associated with decreased OS in metastatic castration-resistant prostate cancer.

PCPro是一种血浆脂质面板，与转移性去势抵抗性前列腺癌的总生存期降低有关。

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).

在这项研究中，我们通过对ENZAMET进行事后分析来评估PCPro与mHSPC临床结果之间的关联，ENZAMET是一项里程碑式的III期试验，比较了恩杂鲁胺与非甾体抗雄激素（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).

PCPro状态是通过液相色谱-质谱分析法对866名参与者（ENZAMET试验队列的77%）的血浆样本进行测定的，这些样本分别在治疗前（n = 866）和首次进展时（n = 282）采集。

Outcomes examined were OS and clinical progression-free survival(clinPFS).

研究考察的结局指标为总生存（OS）和临床无进展生存（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].

基线时PCPro状态为阳性的参与者（13.4%）与PCPro状态为阴性的参与者相比，总生存期（OS）和临床无进展生存期（clinPFS）显著缩短[OS风险比（HR）1.81，95%置信区间（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).

当与关键的临床预后因素一起建模时，PCPro是一个独立的预后因素（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).

与非甾体抗雄激素（NSAA）相比，恩杂鲁胺改善了前列腺癌进展相关蛋白（PCPro）阴性参与者的总生存期（风险比HR 0.61，P < 0.0001），但并未改善PCPro阳性参与者的生存期（HR 1.10，P = 0.69；交互作用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).

无论基线状态如何，进展时PCPro阳性的参与者的总生存期比阴性者短（中位生存期24-28个月对比42-45个月）。

Conclusions

PCPro status is a prognostic biomarker and predictive of the lack of OS benefit from enzalutamide compared with NSAA in mHSPC.

PCPro 状态是一个预后生物标志物，并且预示着与非甾体抗雄激素治疗相比，接受恩杂鲁胺治疗的转移性激素敏感性前列腺癌患者总生存无获益。

These findings provide a rationale for testing therapeutic agents that can modify circulating lipid profiles in mHSPC.

这些发现为测试能够改变循环脂质谱的治疗剂在转移性激素敏感性前列腺癌中的应用提供了理论依据。