Tulane Office of Clinical Research, Tulane School of Medicine, New Orleans, LA, USA.
Tulane School of Medicine, New Orleans, LA, USA.
Oncologist. 2023 Mar 17;28(3):276-e158. doi: 10.1093/oncolo/oyac203.
Black men are at higher risk for prostate cancer death. Previous studies showed a benefit of different therapies, including immune-based therapy, for Black men with metastatic prostate cancer. We sought to explore the efficacy of the PD-L1 inhibitor avelumab in Black men with metastatic castrate-resistant prostate cancer (mCRPC) progressing after abiraterone or enzalutamide.
This pilot phase II study enrolled self-identified Black patients who developed mCRPC on next-generation hormonal therapies (NHTs) abiraterone acetate or enzalutamide (NCT03770455). Enrolled patients received avelumab 10mg/kg IV every 2 weeks while remaining on the same NHTs. The primary endpoint of our study was ≥ 50% reduction in prostate specific antigen (PSA) at ≥8 weeks.
A total of eight patients were enrolled. The median duration on NHTs prior to enrollment was 364 days (95% CI, 260.9-467.1). The median time to initiate avelumab was 8 days (3-14). With a median follow-up of 196 days, no patients achieved the primary endpoint. The median time to PSA progression was 35 days (95 CI%, 0-94.8) and the median time to radiographic and/or clinical progression was 44 days (95 CI%, 0-118.5). The study was closed prematurely due to safety concerns related to the rapid clinical progression observed in the patients enrolled on study.
In conclusion, the addition of avelumab to NHT did not demonstrate clinical activity in Black men with new mCRPC. The unexpected short interval between PSA and radiographic and/or clinical progression observed in this study has potential clinical implications.ClinicalTrials.gov Identifier: NCT03770455 (IND number 139559).
黑人男性患前列腺癌死亡的风险更高。先前的研究表明，对于转移性前列腺癌（mCRPC）进展后的黑人男性，包括免疫治疗在内的不同疗法都有益处。我们试图探讨 PD-L1 抑制剂avelumab 在接受下一代激素治疗（NHT）醋酸阿比特龙或恩扎鲁胺后发生 mCRPC 的黑人男性中的疗效。
这项先导性 II 期研究纳入了自我认定的黑人患者，他们在接受下一代激素治疗（醋酸阿比特龙或恩扎鲁胺）（NCT03770455）后发展为 mCRPC。入组患者在继续使用相同的 NHT 的同时，每 2 周接受 10mg/kg 的avelumab 静脉输注。我们研究的主要终点是在≥8 周时前列腺特异抗原（PSA）降低≥50%。
共入组 8 例患者。入组前接受 NHT 的中位时间为 364 天（95%CI，260.9-467.1）。开始使用 avelumab 的中位时间为 8 天（3-14 天）。中位随访 196 天后，没有患者达到主要终点。PSA 进展的中位时间为 35 天（95%CI%，0-94.8），影像学和/或临床进展的中位时间为 44 天（95%CI%，0-118.5）。由于观察到入组患者的临床快速进展相关的安全性问题，该研究提前终止。
总之，在新诊断的 mCRPC 黑人男性中，avelumab 联合 NHT 并未显示出临床活性。在这项研究中观察到的 PSA 与影像学和/或临床进展之间的时间间隔出乎意料地短，这可能具有临床意义。临床试验标识符：NCT03770455（IND 号 139559）。
