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Lutetium-177–PSMA-617治疗转移性去势抵抗性前列腺癌可延长生存期
作者:小柯机器人 发布时间:2021/6/27 15:52:46

美国杜兰大学Oliver Sartor团队研究了Lutetium-177–PSMA-617治疗转移性去势抵抗性前列腺癌的疗效。相关论文于2021年6月23日发表在《新英格兰医学杂志》上。

虽然最近医学有所进展,但转移性去势抵抗性前列腺癌仍然是致命的。前列腺特异性膜抗原(PSMA)在转移性去势抵抗性前列腺癌中高表达。Lutetium-177 (177Lu) -PSMA-617是一种放射性配体疗法,可将β粒子辐射至表达PSMA的细胞和周围微环境中。

研究组进行了一项国际性、开放性、3期临床试验,招募转移性去势抵抗性前列腺癌患者,这些患者此前至少接受过一种雄激素受体途径抑制剂和一两种紫杉烷方案的治疗,且接受过PSMA阳性镓-68(68Ga)标记PSMA-11正电子发射断层-计算机断层扫描。将患者按2:1随机分组,分别接受177Lu-PSMA-617联合方案允许的标准治疗,或仅接受标准治疗。

方案允许的标准治疗不包括化疗、免疫治疗、镭-223(223Ra) 和试验药物。主要终点是基于影像学的无进展生存期和总生存期,其危险比分别为0.67和0.73。关键次要终点是客观缓解、疾病控制和症状性骨骼事件发生的时间。治疗期间的不良事件是指在最后一次用药后30天内和后续抗癌治疗前发生的不良事件。

2018年6月至2019年10月,1179名筛查患者中共有831名接受了随机分组。两组患者的基线特征保持平衡。中位随访时间为20.9个月。177Lu-PSMA-617联合标准治疗组中基于影像学的中位无进展生存期为8.7个月,显著长于标准治疗组的3.4个月;中位总生存期为15.3个月,显著长于标准治疗组的11.3个月。177Lu-PSMA-617联合标准治疗组的所有关键次要终点均明显优于标准治疗组。177Lu-PSMA-617联合标准治疗组中3级及以上不良事件发生率为52.7%,显著高于标准治疗组的28.0%,但生活质量未受不良影响。

研究结果表明,对于晚期PSMA阳性转移性去势抵抗性前列腺癌患者,177Lu-PSMA-617放射配体治疗联合标准治疗可显著延长基于影像学的无进展生存期和总生存期。

附:英文原文

Title: Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer

Author: Oliver Sartor, M.D.,, Johann de Bono, M.B., Ch.B., Ph.D.,, Kim N. Chi, M.D.,, Karim Fizazi, M.D., Ph.D.,, Ken Herrmann, M.D.,, Kambiz Rahbar, M.D.,, Scott T. Tagawa, M.D.,, Luke T. Nordquist, M.D.,, Nitin Vaishampayan, M.D.,, Ghassan El-Haddad, M.D.,, Chandler H. Park, M.D.,, Tomasz M. Beer, M.D.,, Alison Armour, M.B., Ch.B., M.D.,, Wendy J. Pérez-Contreras, M.P.A.,, Michelle DeSilvio, Ph.D.,, Euloge Kpamegan, Ph.D.,, Germo Gericke, M.D., Ph.D.,, Richard A. Messmann, M.D., M.H.S.,, Michael J. Morris, M.D.,, and Bernd J. Krause, M.D.

Issue&Volume: 2021-06-23

Abstract:

Background

Metastatic castration-resistant prostate cancer remains fatal despite recent advances. Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-resistant prostate cancer. Lutetium-177 (177Lu)–PSMA-617 is a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the surrounding microenvironment.

Methods

We conducted an international, open-label, phase 3 trial evaluating 177Lu-PSMA-617 in patients who had metastatic castration-resistant prostate cancer previously treated with at least one androgen-receptor–pathway inhibitor and one or two taxane regimens and who had PSMA-positive gallium-68 (68Ga)–labeled PSMA-11 positron-emission tomographic–computed tomographic scans. Patients were randomly assigned in a 2:1 ratio to receive either 177Lu-PSMA-617 (7.4 GBq every 6 weeks for four to six cycles) plus protocol-permitted standard care or standard care alone. Protocol-permitted standard care excluded chemotherapy, immunotherapy, radium-223 (223Ra), and investigational drugs. The alternate primary end points were imaging-based progression-free survival and overall survival, which were powered for hazard ratios of 0.67 and 0.73, respectively. Key secondary end points were objective response, disease control, and time to symptomatic skeletal events. Adverse events during treatment were those occurring no more than 30 days after the last dose and before subsequent anticancer treatment.

Results

From June 2018 to mid-October 2019, a total of 831 of 1179 screened patients underwent randomization. The baseline characteristics of the patients were balanced between the groups. The median follow-up was 20.9 months. 177Lu-PSMA-617 plus standard care significantly prolonged, as compared with standard care, both imaging-based progression-free survival (median, 8.7 vs. 3.4 months; hazard ratio for progression or death, 0.40; 99.2% confidence interval [CI], 0.29 to 0.57; P<0.001) and overall survival (median, 15.3 vs. 11.3 months; hazard ratio for death, 0.62; 95% CI, 0.52 to 0.74; P<0.001). All the key secondary end points significantly favored 177Lu-PSMA-617. The incidence of adverse events of grade 3 or above was higher with 177Lu-PSMA-617 than without (52.7% vs. 38.0%), but quality of life was not adversely affected.

Conclusions

Radioligand therapy with 177Lu-PSMA-617 prolonged imaging-based progression-free survival and overall survival when added to standard care in patients with advanced PSMA-positive metastatic castration-resistant prostate cancer.

DOI: 10.1056/NEJMoa2107322

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2107322

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home