在Ⅲ期VISION试验中，前列腺特异性抗原（PSA）下降与转移性去势抵抗性前列腺癌（mCRPC）患者临床结局的相关性——[177Lu]Lu-PSMA-617治疗的研究
Association of Declining Prostate-specific Antigen Levels with Clinical Outcomes in Patients with Metastatic Castration-resistant Prostate Cancer Receiving [177Lu]Lu-PSMA-617 in the Phase 3 VISION Trial
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影响因子:25.2
分区:医学1区 Top / 泌尿学与肾脏学1区
发表日期:2024 Dec
作者:
Andrew J Armstrong, Oliver Sartor, Johann de Bono, Kim Chi, Karim Fizazi, Bernd J Krause, Ken Herrmann, Kambiz Rahbar, Scott T Tagawa, Fred Saad, Tomasz M Beer, Jiwen Wu, Osvaldo Mirante, Michael J Morris
DOI:
10.1016/j.eururo.2024.08.021
摘要
在接受[177Lu]Lu-PSMA-617（177Lu-PSMA-617）靶向放射性配体治疗的前列腺特异性膜抗原（PSMA）阳性转移性去势抵抗性前列腺癌（mCRPC）患者中，PSA下降的预后价值正在研究中。该项对Ⅲ期VISION试验的后续分析旨在评估PSA下降与临床和患者报告结果之间的关联。分析对象为831名曾接受一种或多种雄激素受体途径抑制剂及一至两种紫杉醇治疗的PSMA阳性进行性mCRPC患者，其中551人随机分配接受177Lu-PSMA-617联合方案允许的标准治疗（SoC）。通过多变量Cox比例风险模型分析了放射学无进展生存期（PFS）、总生存期（OS）、放射学客观反应率，以及患者报告的健康相关生活质量（HRQoL）和疼痛的变化，基于基线起未确认的PSA下降幅度进行分组。在第12周前，PSA最高下降≥0-<50%（96/551 [17%]）、≥50-<90%（152/551 [28%]）和≥90%（83/551 [15%]）的患者，患放射学疾病进展或死亡的风险分别减少61%、72%和88%，而死亡风险分别减少51%、70%和87%，相较于PSA升高的患者（160/551 [29%]）。PSA下降幅度越大，放射学反应越频繁，生活质量和疼痛恶化的中位时间也越长。PSA下降的幅度与接受177Lu-PSMA-617联合SoC的mCRPC患者的临床和患者报告结果改善相关。因此，PSA下降在该治疗中具有一定的预后价值。
Abstract
The prognostic value of declining prostate-specific antigen (PSA) levels is under investigation in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) receiving PSMA-targeted radioligand therapy with [177Lu]Lu-PSMA-617 (177Lu-PSMA-617). This post hoc analysis of the phase 3 VISION trial aimed to evaluate associations between PSA decline and clinical and patient-reported outcomes in patients receiving 177Lu-PSMA-617.Of 831 enrolled patients with PSMA-positive progressive mCRPC treated previously with one or more androgen receptor pathway inhibitors and one to two taxanes, 551 were randomised to 177Lu-PSMA-617 plus protocol-permitted standard of care (SoC). Radiographic progression-free survival, overall survival, radiographic objective response rate, and patient-reported health-related quality of life (HRQoL) and pain were analysed in subgroups of patients categorised by the magnitude of unconfirmed PSA decline from baseline.Patients randomised to 177Lu-PSMA-617 with the best PSA declines of ≥0-<50% (96/551 [17%]), ≥50-<90% (152/551 [28%]), and ≥90% (83/551 [15%]) up to and including week 12 had 61%, 72%, and 88% reduced risks of radiographic disease progression or death, and 51%, 70%, and 87% reduced risks of death, respectively, versus those with increased PSA levels (160/551 [29%]), based on hazard ratios in a multivariate Cox proportional hazard model. In patients with greater PSA declines, radiographic responses were more frequent and median time to worsening in HRQoL and pain scores were longer.The magnitude of PSA decline was associated with improvement in clinical and patient-reported outcomes in patients with mCRPC receiving 177Lu-PSMA-617 plus SoC in VISION. PSA decline therefore appears to have a prognostic value during 177Lu-PSMA-617 treatment in this population.