a Sidney Kimmel Center for Prostate and Urologic Cancers, Genitourinary Oncology Service, Department of Medicine , Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College , New York , NY , USA.
Expert Rev Anticancer Ther. 2018 Sep;18(9):823-836. doi: 10.1080/14737140.2018.1503954.
Five new agents have been shown to prolong survival in patients with metastatic castration-resistant prostate cancer, including two targeting androgen receptor signaling (abiraterone acetate plus prednisone; enzalutamide). Recognition that these tumors remain driven by androgen receptor signaling has prompted clinical evaluation of these agents at earlier states in the prostate cancer disease continuum, along with the continued development of new agents targeting this pathway. Areas covered: This article focuses on apalutamide, a next-generation nonsteroidal antiandrogen, with current literature queried in PubMed/Medline. A narrative review strategy describes studies from engineering of the compound through to a 5-year outlook. Expert commentary: In the phase III SPARTAN study, apalutamide significantly improved metastasis-free survival in patients with nonmetastatic castration-resistant prostate cancer - the first treatment approved by the US Food and Drug Administration for this indication. Phase III studies are under way to determine the clinical benefit of apalutamide in other disease states. Given the multiplicity of prostate cancer treatment options now available, there is a need to maximize individual patient benefit through the development and validation of predictive biomarkers of sensitivity to drugs that can be used in real time to determine the optimal sequence and combinations of treatments for patients in need.
五种新药物已被证明可延长转移性去势抵抗性前列腺癌患者的生存期,其中两种靶向雄激素受体信号(醋酸阿比特龙加泼尼松;恩扎鲁胺)。认识到这些肿瘤仍然受雄激素受体信号驱动,促使临床在前列腺癌疾病连续体的早期阶段评估这些药物,同时继续开发靶向该途径的新药物。
本文重点介绍下一代非甾体类抗雄激素药物阿帕鲁胺,在 PubMed/Medline 中查询当前文献。叙述性评论策略描述了从化合物工程到 5 年展望的研究。
在 III 期 SPARTAN 研究中,阿帕鲁胺显著改善了非转移性去势抵抗性前列腺癌患者的无转移生存期-这是美国食品和药物管理局批准的该适应症的第一种治疗方法。正在进行 III 期研究,以确定阿帕鲁胺在其他疾病状态下的临床获益。鉴于目前有多种前列腺癌治疗选择,需要通过开发和验证对药物敏感性的预测性生物标志物来最大限度地提高个体患者的获益,这些生物标志物可实时用于确定有需要的患者的最佳治疗顺序和组合。