Targeted α-Therapy of Metastatic Castration-Resistant Prostate Cancer with 225Ac-PSMA-617:Swimmer-Plot Analysis Suggests Efficacy Regarding Duration of Tumor Control
Targeted α-Therapy of Metastatic Castration-Resistant Prostate Cancer with 225Ac-PSMA-617:Swimmer-Plot Analysis Suggests Efficacy Regarding Duration of Tumor Control
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DOI：
10.2967/jnumed.117.203539
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发表时间：
2018-05-01
影响因子：
9.3
通讯作者：
Morgenstern, Alfred
中科院分区：
文献类型：
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作者：
Kratochwil, Clemens;Bruchertseifer, Frank;Morgenstern, Alfred
本评价的目的是在回顾性分析的患者组中确定Ac-225标记的前列腺特异性膜抗原（PSMA）-617治疗的疗效的首要指标。研究方法：选择40名患有转移性去势抵抗性前列腺癌的患者以2个月间隔用三个100 kBq/kg周期的Ac-225-PSMA- 617治疗。每4周检测一次前列腺特异性抗原（PSA）和血细胞计数。PSMA PET/CT或PSMA SPECT/CT用于基线分期和第6个月的成像随访。随访包括PSA缓解持续时间和第6个月的放射学无进展生存期。审查既往治疗线持续时间的患者病史，并使用游泳图对PSMA治疗与既往治疗方式的肿瘤控制持续时间进行个体内比较。结果：40例患者中有31例按方案治疗。5例患者因无应答而停止治疗，4例因口干而停止治疗。在存活至少8周的38例患者中，24例（63%）PSA下降超过50%，33例（87%）有任何程度的PSA反应。在Ac-225-PSMA 617的最后一线治疗下，肿瘤控制的中位持续时间为9.0个月; 5名患者的持续反应超过2年。由于所有患者均为晚期疾病，该结果与早期疾病相关的肿瘤控制率相比具有优势;最常见的既往一线、二线、三线和四线治疗分别为阿比特龙（中位持续时间10.0个月）、多西他赛（6.5个月）、Enzalutamide（6.5个月）和卡巴他赛（6.0个月）。结论：替代参数的阳性响应表明Ac-225-PSMA-617具有显著的抗肿瘤活性。Swimmer图分析表明肿瘤控制的持续时间很有希望，特别是考虑到所选晚期患者的不良预后。口干症是患者停止治疗或拒绝额外给药的主要原因，与无应答处于相同的维度;这一发现表明，可能需要进一步修改治疗方案的副作用，以进一步提高治疗范围。
The aim of this evaluation was to identify the first indicators of efficacy for Ac-225-labeled prostate-specific membrane antigen (PSMA)-617 therapy in a retrospectively analyzed group of patients. Methods: Forty patients with metastatic castration-resistant prostate cancer were selected for treatment with three 100 kBq/kg cycles of Ac-225-PSMA- 617 at 2-mo intervals. Prostate-specific antigen (PSA) and blood cell count were measured every 4 wk. PSMA PET/CT or PSMA SPECT/CT were used for baseline staging and imaging follow-up at month 6. Follow-up included the duration of PSA response and radiologic progression-free survival at month 6. Patient histories were reviewed for the duration of previous treatment lines, and a swimmer plot was used to intraindividually compare the duration of tumor control by PSMA therapy versus prior treatment modalities. Results: Thirty-one of 40 patients were treated per protocol. Five patients discontinued treatment because of nonresponse, and 4 because of xerostomia. Of the 38 patients surviving at least 8 wk, 24 (63%) had a PSA decline of more than 50%, and 33 (87%) had a PSA response of any degree. The median duration of tumor control under Ac-225-PSMA617 last-line therapy was 9.0mo; 5 patients had an enduring response of more than 2 y. Because all patients had advanced disease, this result compares favorably with the tumor control rates associated with earlier-phase disease; the most common preceding first-, second-, third-, and fourth-line therapies were abiraterone (median duration 10.0 mo), docetaxel (6.5 mo), enzalutamide (6.5 mo), and cabazitaxel (6.0 mo), respectively. Conclusion: A positive response for surrogate parameters demonstrates remarkable antitumor activity for Ac-225-PSMA-617. Swimmer-plot analysis indicates a promising duration of tumor control, especially considering the un-favorable prognostic profile of the selected advanced-stage patients. Xerostomia was the main reason patients discontinued therapy or refused additional administrations and was in the same dimension as nonresponse; this finding indicates that further modifications of the treatment regimen with regard to side effects might be necessary to further enhance the therapeutic range.