Rahbar Kambiz, Ahmadzadehfar Hojjat, Kratochwil Clemens, Haberkorn Uwe, Schäfers Michael, Essler Markus, Baum Richard P, Kulkarni Harshad R, Schmidt Matthias, Drzezga Alexander, Bartenstein Peter, Pfestroff Andreas, Luster Markus, Lützen Ulf, Marx Marlies, Prasad Vikas, Brenner Winfried, Heinzel Alexander, Mottaghy Felix M, Ruf Juri, Meyer Philipp Tobias, Heuschkel Martin, Eveslage Maria, Bögemann Martin, Fendler Wolfgang Peter, Krause Bernd Joachim
Department of Nuclear Medicine, University Hospital Muenster, Muenster, Germany
Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.
J Nucl Med. 2017 Jan;58(1):85-90. doi: 10.2967/jnumed.116.183194. Epub 2016 Oct 20.
Lu-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine, a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of Lu-PSMA-617 in a large cohort of patients.
One hundred forty-five patients (median age, 73 y; range, 43-88 y) with mCRPC were treated with Lu-PSMA-617 in 12 therapy centers between February 2014 and July 2015 with 1-4 therapy cycles and an activity range of 2-8 GBq per cycle. Toxicity was categorized by the common toxicity criteria for adverse events (version 4.0) on the basis of serial blood tests and the attending physician's report. The primary endpoint for efficacy was biochemical response as defined by a prostate-specific antigen decline ≥ 50% from baseline to at least 2 wk after the start of RLT.
A total of 248 therapy cycles were performed in 145 patients. Data for biochemical response in 99 patients as well as data for physician-reported and laboratory-based toxicity in 145 and 121 patients, respectively, were available. The median follow-up was 16 wk (range, 2-30 wk). Nineteen patients died during the observation period. Grade 3-4 hematotoxicity occurred in 18 patients: 10%, 4%, and 3% of the patients experienced anemia, thrombocytopenia, and leukopenia, respectively. Xerostomia occurred in 8%. The overall biochemical response rate was 45% after all therapy cycles, whereas 40% of patients already responded after a single cycle. Elevated alkaline phosphatase and the presence of visceral metastases were negative predictors and the total number of therapy cycles positive predictors of biochemical response.
The present retrospective multicenter study of Lu-PSMA-617 RLT demonstrates favorable safety and high efficacy exceeding those of other third-line systemic therapies in mCRPC patients. Future phase II/III studies are warranted to elucidate the survival benefit of this new therapy in patients with mCRPC.
镥标记的PSMA - 617是一种有前景的新型治疗药物，用于转移性去势抵抗性前列腺癌（mCRPC）患者的放射性配体治疗（RLT）。由德国核医学协会发起，2015年开始进行一项回顾性多中心数据分析，以评估镥 - PSMA - 617在一大群患者中的疗效和安全性。
2014年2月至2015年7月期间，145例mCRPC患者（中位年龄73岁；范围43 - 88岁）在12个治疗中心接受镥 - PSMA - 617治疗，治疗周期为1 - 4个，每个周期的活度范围为2 - 8 GBq。根据连续血液检测和主治医生报告，按照不良事件通用毒性标准（第4.0版）对毒性进行分类。疗效的主要终点是生化反应，定义为前列腺特异性抗原从基线下降≥50%，且在RLT开始后至少2周。
145例患者共进行了248个治疗周期。分别获得了99例患者的生化反应数据以及145例和121例患者的医生报告和基于实验室的毒性数据。中位随访时间为16周（范围2 - 30周）。19例患者在观察期内死亡。18例患者发生3 - 4级血液毒性：分别有10%、4%和3%的患者出现贫血、血小板减少和白细胞减少。8%的患者出现口干。所有治疗周期后的总体生化反应率为45%，而40%的患者在单个周期后即有反应。碱性磷酸酶升高和内脏转移的存在是生化反应的负性预测因素；治疗周期总数是生化反应的正性预测因素。
目前关于镥 - PSMA - 617 RLT的回顾性多中心研究表明，其安全性良好且疗效高，超过了mCRPC患者其他三线全身治疗的疗效。未来有必要开展II/III期研究，以阐明这种新疗法对mCRPC患者的生存获益。
