Introduction and aim

Radioligand therapy (RLT) with ¹⁷⁷Lu-labelled prostate specific membrane antigen ([¹⁷⁷Lu]Lu-PSMA-X, referring with “PSMA-X” to a generic PSMA chemical compound) inhibitors has emerged as a viable treatment option in metastatic castration resistant prostate cancer patients having previously progressed on taxane and androgen receptor inhibitors. The aim of this study was to perform a systematic review and meta-analysis to assess the therapeutic efficacy of [¹⁷⁷Lu]Lu-PSMA-X compared to taxane chemotherapy in taxane-chemo-naïve patients with metastatic castration-resistant prostate cancer.

Materials and methods

Searches in several bibliographic databases were made using relevant key words, and articles published up to March 2024 were included. The endpoints included prostate specific antigen (PSA) response rate (RR), progression-free survival, and overall survival. Individual patient data were pooled when feasible. PSA50 was defined as the median proportion of patients achieving at least a 50% decline in serum PSA from baseline. A meta-analysis of the PSA50 response rate (proportion meta-analysis) was performed, generating pooled estimates and 95% confidence intervals (95% CI).

Results

From the initially selected 8,414 studies published between 2019 and 2023, 24 were included in the [¹⁷⁷Lu]Lu-PSMA-X treated group and 17 in the taxane treated group. Our findings show that [¹⁷⁷Lu]Lu-PSMA-X RLT yielded comparable PSA50 responses in taxane-naïve patients versus those receiving taxane chemotherapy, despite considerable study heterogeneity. Notably, the taxane-naïve group had more extensive pretreatment.

Conclusions

This meta-analysis combines the largest cohorts of taxane-naïve mCRPC patients treated with [¹⁷⁷Lu]Lu-PSMA-X RLT and taxane-treated mCRPC. It underscores similar PSA50 response rates in both groups, suggesting a potential role for [¹⁷⁷Lu]Lu-PSMA-X RLT in taxane-naïve patients who cannot or choose not to undergo chemotherapy.

中文翻译：

---

评估 [177Lu]Lu-PSMA-X 与紫杉烷化疗相比对转移性去势抵抗性前列腺癌初治患者的治疗效果：系统评价和荟萃分析

 简介和目标

使用 ¹⁷⁷Lu 标记的前列腺特异性膜抗原（[¹⁷⁷Lu]Lu-PSMA-X，与“PSMA-X”一起指通用 PSMA 化合物）抑制剂的放射配体疗法 （RLT） 已成为转移性去势抵抗性前列腺癌患者的可行治疗选择，这些患者既往在紫杉烷类和雄激素受体抑制剂治疗后出现进展。本研究的目的是进行系统评价和荟萃分析，以评估 [¹⁷⁷Lu]Lu-PSMA-X 与紫杉烷化疗相比对转移性去势抵抗性前列腺癌未接受过化疗治疗的疗效。

 材料和方法

使用相关关键词在几个书目数据库中进行检索，并纳入了截至 2024 年 3 月发表的文章。终点包括前列腺特异性抗原 （PSA） 反应率 （RR） 、无进展生存期和总生存期。在可行的情况下，将个体患者数据合并。PSA50 定义为血清 PSA 较基线至少下降 50% 的患者的中位比例。对 PSA50 反应率进行了荟萃分析（比例荟萃分析），生成合并估计值和 95% 置信区间 （95% CI）。

 结果

在 2019 年至 2023 年间发表的最初选择的 8,414 项研究中，24 项被纳入 [¹⁷⁷Lu]Lu-PSMA-X 处理组，17 项被纳入紫杉烷处理组。我们的研究结果表明，尽管研究存在相当大的异质性，但 [¹⁷⁷Lu]Lu-PSMA-X RLT 在未接受过紫杉烷类药物的患者与接受紫杉烷类化疗的患者中产生了相当的 PSA50 反应。值得注意的是，紫杉烷初治组进行了更广泛的预处理。

 结论

本荟萃分析结合了接受 [¹⁷⁷Lu]Lu-PSMA-X RLT 和紫杉烷治疗 mCRPC 的最大未接受过紫杉烷类治疗的 mCRPC 患者队列。它强调了两组相似的 PSA50 反应率，表明 [¹⁷⁷Lu]Lu-PSMA-X RLT 在不能或选择不接受化疗的紫杉烷初治患者中具有潜在作用。