Defining the Position of [¹⁷⁷Lu]Lu-PSMA Radioligand Therapy in the Treatment Landscape of Metastatic Castration-Resistant Prostate Cancer: A Meta-analysis of Clinical Trials.

IF 4.4 3区医学 Q2 ONCOLOGY Targeted Oncology Pub Date : 2025-01-01 Epub Date: 2024-11-29 DOI:10.1007/s11523-024-01117-1

Chiara Ciccarese, Matteo Bauckneht, Luca Zagaria, Giuseppe Fornarini, Viria Beccia, Francesco Lanfranchi, Germano Perotti, Giada Pinterpe, Fortuna Migliaccio, Giampaolo Tortora, Lucia Leccisotti, Gianmario Sambuceti, Alessandro Giordano, Orazio Caffo, Roberto Iacovelli

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Abstract

Background: In recent years, theranostics has become a promising approach for treating metastatic castration-resistant prostate cancer (mCRPC), with trials investigating targeted radioligand therapy, particularly using prostate-specific membrane antigen labeled with lutetium-177 ([¹⁷⁷Lu]Lu-PSMA). The proper position of [¹⁷⁷Lu]Lu-PSMA in the therapeutic algorithm of mCRPC is yet to be identified.

Design, setting, and participants: We conducted a systematic review and meta-analysis of phase II/III randomized controlled trials to assess the efficacy of [¹⁷⁷Lu]Lu-PSMA in treating mCRPC. Study endpoints included radiographic progression-free survival (rPFS), prostate-specific antigen-PFS, objective response rate, and overall survival.

Outcome measurements and statistical analysis: Data were extracted according to the PRISMA statement. Summary hazard ratios (HRs) were calculated using random- or fixed-effects models. Statistical analyses were performed with RevMan software (v.5.2.3).

Results: [¹⁷⁷Lu]Lu-PSMA reduced the risk of rPFS (HR 0.55; 95% confidence interval [CI] 0.43-0.71; p < 0.00001) and prostate-specific antigen-PFS (HR 0.53; 95% CI 0.41-0.67; p < 0.00001), and improved the objective response rate compared with control therapies (response rate 3.55; 95% CI 1.91-6.60; p < 0.0001), whereas no significant cumulative effect on overall survival was documented (HR 0.92; 95% CI 0.65-1.31; p = 0.63). Notably, in a dedicated subanalysis, comparable effects on rPFS were observed when [¹⁷⁷Lu]Lu-PSMA was compared with active therapy.

Conclusion: [¹⁷⁷Lu]Lu-PSMA has a favorable impact on the radiographic and biochemical control of mCRPC and represents a potential treatment in a scenario where other valuable options are available. Further efforts are required to identify clinical and molecular markers necessary for proper patient stratification.

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确定[177Lu]Lu-PSMA放射配体治疗在转移性去势抵抗性前列腺癌治疗中的地位：临床试验的荟萃分析。

背景：近年来，治疗已成为治疗转移性去势抵抗性前列腺癌（mCRPC）的一种有前景的方法，研究了靶向放射配体治疗，特别是使用黄体-177标记的前列腺特异性膜抗原（[177Lu]Lu-PSMA）。[177Lu]Lu-PSMA在mCRPC治疗算法中的正确位置尚未确定。设计、环境和参与者：我们对II/III期随机对照试验进行了系统回顾和荟萃分析，以评估[177Lu]Lu-PSMA治疗mCRPC的疗效。研究终点包括放射无进展生存期（rPFS）、前列腺特异性抗原pfs、客观缓解率和总生存期。结果测量和统计分析：根据PRISMA声明提取数据。使用随机或固定效应模型计算总风险比（hr）。采用RevMan软件（v.5.2.3）进行统计分析。结果：[177Lu]Lu-PSMA降低了rPFS的风险(HR 0.55；95%置信区间[CI] 0.43-0.71；p < 0.00001)和前列腺特异性抗原pfs (HR 0.53；95% ci 0.41-0.67；P < 0.00001)，客观有效率较对照治疗提高(有效率3.55；95% ci 1.91-6.60；p < 0.0001)，而总生存期无显著累积效应(HR 0.92；95% ci 0.65-1.31；P = 0.63)。值得注意的是，在一项专门的亚分析中，当[177Lu]Lu-PSMA与积极治疗相比，对rPFS的影响可比较。结论：[177Lu]Lu-PSMA对mCRPC的放射学和生化控制有良好的影响，在其他有价值的选择可用的情况下，它代表了一种潜在的治疗方法。需要进一步努力确定临床和分子标记物，以进行适当的患者分层。

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来源期刊

Targeted Oncology 医学-肿瘤学

CiteScore

8.40

自引率

3.70%

发文量

审稿时长

>12 weeks

期刊介绍： Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes: Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches. Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways. Current Opinion articles that place interesting areas in perspective. Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations. Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement. Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.