Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Nuclear Medicine Operative Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Br J Cancer. 2021 Oct;125(9):1226-1232. doi: 10.1038/s41416-021-01508-5. Epub 2021 Jul 31.
In a Phase 2 clinical trial, we aimed to determine the lutetium-177 [Lu]-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).
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 Lu-PSMA-617.
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.
Plasma AR status helped to indicate mCRPC with early resistance to Lu-PSMA-617.
NCT03454750.
在一项 2 期临床试验中，我们旨在确定镥-177[Lu]-PSMA-617 的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（mCRPC）患者中的临床应用价值。
我们测定了预处理血浆样本中的 AR 拷贝数。我们使用逻辑回归来估计比值比（OR）和 95%置信区间（95%CI），以评估 AR 状态的独立相关性，并评估定义为 Lu-PSMA-617 治疗开始后 4 个月内发生治疗中断的早期进展性疾病（PD）患者。
15 例中有 12 例（80%）AR 基因获得和 25 例中无 AR 基因获得的 5 例（20%）患者出现早期 PD（p=0.0002）。无 PSA 反应患者 AR 获得的 OR 为 3.69（95%CI 0.83-16.36，p=0.085）。早期 PD 患者 AR 获得的 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 获得的患者 OS 显著缩短（7.4 与 19.1 个月，p=0.020）。没有因不良反应而中断治疗的报道。
血浆 AR 状态有助于预测 Lu-PSMA-617 早期耐药的 mCRPC。
NCT03454750。
