Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer.
Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer.
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Lutetium-177-PSMA-617 用于治疗转移性去势抵抗性前列腺癌。
DOI：
10.1056/nejmoa2107322
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发表时间：
2021-09-16
期刊：
影响因子：
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通讯作者：
VISION Investigators
中科院分区：
文献类型：
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作者：
Sartor O;de Bono J;Chi KN;Fizazi K;Herrmann K;Rahbar K;Tagawa ST;Nordquist LT;Vaishampayan N;El-Haddad G;Park CH;Beer TM;Armour A;Pérez-Contreras WJ;DeSilvio M;Kpamegan E;Gericke G;Messmann RA;Morris MJ;Krause BJ;VISION Investigators
尽管最近取得了进展，但耐去势转移性前列腺癌仍然是致命的。前列腺特异性膜抗原(PSMA)在转移性去势抵抗前列腺癌中高表达。Lu-177(177Lu)-PSMA-617是一种放射配基疗法，可向表达PSMA的细胞和周围微环境传递贝塔粒子辐射。我们进行了一项国际开放标签3期试验，评估了之前接受过至少一种雄激素受体途径抑制剂和一种或两种紫杉烷方案治疗的转移性去势抵抗前列腺癌患者的177Lu-PSMA-617，这些患者进行了PSMA-68(68Ga)标记的PSMA-11正电子发射断层扫描。患者按2：1的比例随机分配，接受177Lu-PSMA-617(每6周7.4GBq，共4至6个周期)加方案允许的标准护理或仅接受标准护理。协议允许的标准护理不包括化疗、免疫治疗、Re-223(223Ra)和研究药物。替代的主要终点是基于成像的无进展存活率和总存活率，风险比分别为0.67和0.73。关键的次要终点是客观反应、疾病控制和出现症状性骨骼事件的时间。治疗期间的不良事件是指在最后一次服药后30天内和随后的抗癌治疗之前发生的不良事件。从2018年6月至2019年10月中旬，在1179名筛查患者中，共有831人接受了随机分组。患者的基线特征在两组之间是平衡的。中位随访时间为20.9个月。与标准护理相比，177Lu-PSMA-617加标准护理显著延长了基于成像的无进展存活期(中位数为8.7mo；进展或死亡的风险比为0.40；99.2%可信区间[CI]，0.29vs.0.57；P<；0.001)和总存活率(中位数15.3mo；死亡风险比0.62月；95%CI0.52至0.74；P<；0.001)。所有关键次级终点均明显偏向177Lu-PSMA-617。使用177Lu-PSMA-617的患者3级及以上不良事件发生率高于未使用的患者(52.7%vs.38.0%)，但对生活质量无不良影响。在标准治疗中，使用177Lu-PSMA-617放射配基治疗可延长晚期PSMA阳性转移性去势耐受前列腺癌患者基于成像的无进展生存期和总生存期。(资金来自诺华公司Endocyte；Vision ClinicalTrials.gov编号，NCT03511664。)
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. 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. 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. 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. (Funded by Endocyte, a Novartis company; VISION ClinicalTrials.gov number, NCT03511664.)