Background

In a Phase 2 clinical trial, we aimed to determine the lutetium-177 [¹⁷⁷Lu]-PSMA-617 activity and the clinical utility of levels of plasma androgen receptor (AR) gene in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC).

Methods

We determined AR copy number in pretreatment plasma samples. We used logistic regression to estimate the odds ratio (OR) and 95% confidence intervals (95% CIs) in order to evaluate the independent relevance of AR status and to evaluate patients with early progressive disease (PD) defined as treatment interruption occurring within 4 months after the start of ¹⁷⁷Lu-PSMA-617.

Results

Twelve of the 15 (80%) with AR gene gain and 5 of the 25 (20%) patients with no gain of AR had early PD (p = 0.0002). The OR for patients without PSA response having AR gain was 3.69 (95% CI 0.83–16.36, p = 0.085). The OR for patients with early PD having AR gain was 16.00, (95% CI 3.23–79.27, p = 0.0007). Overall, median PFS and OS were 7.5 and 12.4 months, respectively. AR-gained had a significant shorter OS compared to AR-normal patients (7.4 vs 19.1 months, p = 0.020). No treatment interruptions due to adverse effects were reported.

Discussion

Plasma AR status helped to indicate mCRPC with early resistance to ¹⁷⁷Lu-PSMA-617.

Trial registration

NCT03454750.

中文翻译：

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转移性去势抵抗性前列腺癌中循环雄激素受体基因扩增和对 177Lu-PSMA-617 的耐药性：2 期试验结果

背景

在一项 2 期临床试验中，我们旨在确定 lutetium-177 [ ¹⁷⁷ Lu]-PSMA-617 活性和血浆雄激素受体 (AR) 基因水平在经过大量预处理的转移性去势抵抗性前列腺癌患者中的临床应用。 mCRPC)。

方法

我们确定了预处理血浆样品中的 AR 拷贝数。我们使用逻辑回归来估计优势比 (OR) 和 95% 置信区间 (95% CI) 以评估 AR 状态的独立相关性并评估早期进展性疾病 (PD) 定义为治疗中断发生在 4 ¹⁷⁷ Lu-PSMA-617开始几个月后。

结果

15 名（80%）AR基因增加的患者中有 12 名（80%）和 25 名（20%）没有AR增加的患者中有 5 名早期 PD（p  = 0.0002）。没有 PSA 反应且AR增加的患者的 OR 为 3.69（95% CI 0.83-16.36，p  = 0.085）。AR增加的早期 PD 患者的 OR 为16.00，（95% CI 3.23-79.27，p  = 0.0007）。总体而言，中位 PFS 和 OS 分别为 7.5 个月和 12.4 个月。与AR正常患者相比， AR患者的 OS 显着缩短（7.4 个月 vs 19.1 个月，p  = 0.020）。没有报告因不良反应而中断治疗。

讨论

血浆AR状态有助于表明 mCRPC 对¹⁷⁷ Lu-PSMA-617 具有早期耐药性。

试用注册

NCT03454750。