Koshkin Vadim S, Small Eric J
Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, 550 16th Street, Box 3211, San Francisco, CA 94158, USA.
Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Ther Adv Urol. 2018 Nov 11;10(12):445-454. doi: 10.1177/1756287218811450. eCollection 2018 Dec.
Apalutamide (ARN-509) is a second-generation androgen receptor (AR) antagonist that was developed to inhibit AR-mediated prostate cancer cell proliferation. Following the initial promising clinical efficacy results in phase I and II clinical trials of patients with metastatic castrate-resistant prostate cancer (CRPC), apalutamide has been investigated in several phase III trials. Particular interest has focused on the development of effective therapy for the prevention of disease progression in patients with nonmetastatic (nm or M0) CRPC, especially patients who have a rapid prostate-specific antigen (PSA) doubling time that is indicative of shorter bone metastasis-free survival and associated with significant morbidity and mortality. The results from the phase III SPARTAN trial were recently published and reported a significant benefit of apalutamide relative to placebo in patients with nmCRPC and a high risk of metastatic progression. The study noted marked improvement in the primary endpoint of metastasis-free survival as well as several relevant secondary clinical endpoints, including time to symptomatic progression. These results led to the United States Food and Drug Administration (US FDA) approval of apalutamide in the nmCRPC setting in February 2018. This review summarizes the clinical development of apalutamide, culminating with the pivotal SPARTAN trial as well as other phase III trials which may further expand potential indications for this agent in the near future.
阿帕鲁胺（ARN-509）是一种第二代雄激素受体（AR）拮抗剂，开发用于抑制AR介导的前列腺癌细胞增殖。在转移性去势抵抗性前列腺癌（CRPC）患者的I期和II期临床试验取得初步令人鼓舞的临床疗效结果后，阿帕鲁胺已在多项III期试验中进行研究。特别关注的是开发有效疗法，用于预防非转移性（nm或M0）CRPC患者的疾病进展，尤其是那些前列腺特异性抗原（PSA）加倍时间短，表明无骨转移生存期较短且伴有显著发病率和死亡率的患者。III期SPARTAN试验的结果最近发表，报告了阿帕鲁胺相对于安慰剂在nmCRPC和高转移进展风险患者中的显著益处。该研究指出，无转移生存期的主要终点以及几个相关的次要临床终点，包括有症状进展时间，均有显著改善。这些结果导致美国食品药品监督管理局（US FDA）于2018年2月批准阿帕鲁胺用于nmCRPC治疗。本综述总结了阿帕鲁胺的临床开发情况，重点介绍了关键的SPARTAN试验以及其他III期试验，这些试验可能在不久的将来进一步扩大该药物的潜在适应症。
