一线雄激素受体通路抑制剂（ARPI）治疗后，镥-177前列腺特异性膜抗原（PSMA）放射性配体疗法用于初治的一线和二线转移性去势抵抗性前列腺癌。
Lutetium-177 PSMA radioligand therapy in taxan-naive first- and second-line metastatic castration resistant prostate cancer after first-line ARPI therapy.
作者信息
Wenzel Mike, Hoeh Benedikt, Siech Carolin, Koll Florestan, Humke Clara, Groener Daniel, Steuber Thomas, Graefen Markus, Maurer Tobias, Banek Severine, Chun Felix K H, Mandel Philipp
机构信息
Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt Am Main, Frankfurt, Germany.
Department of Nuclear Medicine, University Hospital Frankfurt, Goethe University Frankfurt Am Main, Frankfurt, Germany.
出版信息
Eur J Nucl Med Mol Imaging. 2025 May;52(6):2015-2022. doi: 10.1007/s00259-025-07076-7. Epub 2025 Jan 13.
PURPOSE
Lutetium-177 Prostate-specific membrane antigen (Lu-PSMA) radioligand therapy is EMA-approved for metastatic castration resistant prostate cancer (mCRPC) after androgen receptor pathway inhibition (ARPI) and taxan-based chemotherapy. However, its effect in taxan-naïve patients is under current investigation.
METHODS
We relied on the FRAMCAP database to elaborate Lu-PSMA therapy outcomes of progression-free (PFS) and overall (OS) in taxan-naïve mCRPC patients after previous ARPI treatment. Comparison was made against current standard of care with ARPI or docetaxel, irrespective of the previous used staging modality.
RESULTS
Of 269 patients, 11% received Lu-PSMA in first/second-line mCRPC vs. 57% ARPI vs. 33% docetaxel. Mostly no significant baseline differences between Lu-PSMA and ARPI patients were observed, while Lu-PSMA patients were significantly older, received less systematic treatments and ECOG1-2 proportions were higher, relative to docetaxel patients. In PFS (13.3 vs. 8.2 months, hazard ratio [HR]: 0.70, p = 0.16) and OS analyses (68.9 vs. 39.1 months, HR: 0.64, p = 0.2), Lu-PSMA was numerically more favorable than ARPI. In additional multivariable Cox regression models, Lu-PSMA was significant better regarding PFS and OS, relative to ARPI (both p < 0.05). Compared to docetaxel, also significant better PFS (13.3 vs. 8.1 months, HR: 0.46) and OS (68.9 vs. 27.3 months, HR: 0.34, both p < 0.01) was observed for Lu-PSMA treatment. The OS advantage was also observed after multivariable adjustment (p < 0.01).
CONCLUSION
This retrospective single-center study including a substantial proportion of patients with treatment preference for Lu-PSMA suggests that Lu-PSMA therapy provides significantly more favorable PFS and OS outcomes in taxan-naïve mCRPC patients after previous ARPI treatment, relative to ARPI or docetaxel treatment and may be considered as an early mCRPC treatment option.
目的
镥-177前列腺特异性膜抗原（Lu-PSMA）放射性配体疗法已获欧洲药品管理局（EMA）批准，用于雄激素受体途径抑制（ARPI）和紫杉烷类化疗后的转移性去势抵抗性前列腺癌（mCRPC）。然而，其在未接受过紫杉烷治疗的患者中的疗效目前正在研究中。
方法
我们依靠FRAMCAP数据库，阐述了未接受过紫杉烷治疗的mCRPC患者在接受过ARPI治疗后，接受Lu-PSMA治疗的无进展生存期（PFS）和总生存期（OS）结果。与当前使用ARPI或多西他赛的标准治疗进行比较，无论之前使用的分期方式如何。
结果
在269例患者中，11%在mCRPC一线/二线治疗中接受了Lu-PSMA治疗，57%接受了ARPI治疗，33%接受了多西他赛治疗。在Lu-PSMA组和ARPI组患者之间，大多未观察到显著的基线差异，而与多西他赛组患者相比，Lu-PSMA组患者年龄显著更大，接受的系统治疗更少，且ECOG 1-2比例更高。在PFS分析中（13.3个月对8.2个月，风险比[HR]：0.70，p = 0.16）和OS分析中（68.9个月对39.1个月，HR：0.64，p = 0.2），Lu-PSMA在数值上比ARPI更有利。在额外的多变量Cox回归模型中，相对于ARPI，Lu-PSMA在PFS和OS方面显著更好（均p < 0.05）。与多西他赛相比，Lu-PSMA治疗在PFS（13.3个月对8.1个月，HR：0.46）和OS（68.9个月对27.3个月，HR：0.34，均p < 0.01）方面也显著更好。在多变量调整后也观察到了OS优势（p < 0.01）。
结论
这项回顾性单中心研究纳入了相当比例倾向于Lu-PSMA治疗的患者，表明相对于ARPI或多西他赛治疗，Lu-PSMA疗法在先前接受过ARPI治疗的未接受过紫杉烷治疗的mCRPC患者中，能提供显著更优的PFS和OS结果，可被视为mCRPC的一种早期治疗选择。
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