Phase II Study of Ipilimumab in Men With Metastatic Prostate Cancer With an Incomplete Response to Androgen Deprivation Therapy
Phase II Study of Ipilimumab in Men With Metastatic Prostate Cancer With an Incomplete Response to Androgen Deprivation Therapy
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DOI：
10.3389/fonc.2020.01381
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发表时间：
2020-08-07
影响因子：
4.7
通讯作者：
Beer, Tomasz M.
中科院分区：
文献类型：
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作者：
Graff, Julie N.;Stein, Mark N.;Beer, Tomasz M.
背景：免疫检查点抑制剂的 3 期研究尚未显示前列腺癌的生存获益，但一些患者具有显着的抗癌反应。 患者和方法：我们评估了 CTLA-4 靶向药物伊匹单抗 (ipilimumab) 在对单独初始雄激素剥夺疗法 (ADT) 生化反应不完全的转移性前列腺癌患者中的疗效。入组了 10 名患者，每名患者接受伊匹单抗 10 mg/kg（每 3 周一次，最多 4 剂）治疗，对于非进展患者，每 12 周接受伊匹单抗维持治疗。主要终点是 PSA 检测不到的患者比例。总样本量为 30 名患者，但由于徒劳，计划对 10 名患者进行中期分析。如果 10 名患者均未达到不可检测的 PSA，则研究将停止。 结果：研究在中期分析时停止，因为 10 名患者均未达到主要终点，但 30% 的患者表现出 PSA 降低 > 50%，其中一名患者的 PSA 降低 > 90%。通过质谱流式细胞术检查的外周血单核细胞 (PBMC) 显示，具有临床反应的患者效应记忆 T 细胞亚群以及 T-bet 的 T 细胞表达增加，表明诱导了 Th1 反应。结论：这项研究提供了进一步的证据，表明伊匹单抗在某些前列腺癌患者中具有活性，并为未来研究的发展提供了进一步的理论依据，这些研究旨在确定 CPRC 患者亚群，这些患者更有可能从 CPRC 治疗中获益。伊匹单抗。对实践的影响：没有足够的证据表明在常规实践中使用伊匹单抗治疗前列腺癌。
Background: Phase 3 studies of immune checkpoint inhibitors have not shown a survival benefit in prostate cancer, but some patients have a profound anticancer response.Patients and Methods: We evaluated the efficacy of the CTLA-4 targeted agent, ipilimumab, in metastatic prostate cancer patients who had an incomplete biochemical response to initial androgen deprivation therapy (ADT) alone. Ten patients were enrolled, each treated with ipilimumab 10 mg/kg (every 3 weeks for up to 4 doses) with maintenance ipilimumab every 12 weeks for non-progressing patients. The primary endpoint was proportion of patients with an undetectable PSA. The total sample size was 30 patients, but there was an interim analysis planned at 10 for futility. If none of the 10 patients achieved an undetectable PSA, the study would be halted.Results: The study was halted at the interim analysis as none of the 10 patients achieved the primary endpoint, but 30% of patients demonstrated a >50% reduction in PSA, with one patient achieving a >90% reduction in PSA. Peripheral blood mononuclear cells (PBMC) examined by mass cytometry showed that patients with clinical responses had an increase in effector memory T-cell subsets as well as an increase in T-cell expression of T-bet, suggesting induction of a Th1 response.Conclusions: This study provides further evidence that ipilimumab has activity in some patients with prostate cancer and provides further rationale for the development of future studies aimed at identifying a subset of patients with CPRC that are more likely to derive a benefit from treatment with ipilimumab.Implications for Practice: There is insufficient evidence to use ipilimumab in prostate cancer in routine practice.