May Megan B, Glode Ashley E
Department of Pharmacy, Baptist Health Lexington, Lexington, KY, USA.
Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Boulder, CO, USA.
J Oncol Pharm Pract. 2019 Dec;25(8):1968-1978. doi: 10.1177/1078155219864424. Epub 2019 Jul 30.
Apalutamide is a competitive inhibitor of the androgen receptor and binds directly to the ligand-binding domain. The US Food and Drug Administration approved apalutamide on 14 February 2018 for use in patients with nonmetastatic castration-resistant prostate cancer based upon results from the phase III SPARTAN trial demonstrating significantly longer metastasis-free survival over placebo. The SPARTAN trial evaluated 1207 patients with nonmetastatic castration-resistant prostate cancer who were randomized 2:1 to apalutamide or placebo in combination with androgen deprivation therapy. Patients who received apalutamide experienced statistically significantly longer metastasis-free survival (40.5 versus 16.2 months, hazard ratio 0.28 (95% confidence interval = 0.23-0.35); P < 0.0001), which was the major efficacy outcome. Rash, hypothyroidism, and fracture were reported to occur more frequently with apalutamide than placebo. Based upon these results, apalutamide was deemed a safe and effective treatment option for patients with nonmetastatic castration-resistant prostate cancer. Clinical trials are ongoing to expand its indication in the metastatic setting, and identify additional roles for apalutamide in the management of prostate cancer such as in the castrate-sensitive metastatic setting.
阿帕鲁胺是雄激素受体的竞争性抑制剂，可直接与配体结合域结合。基于III期SPARTAN试验结果显示，与安慰剂相比，无转移生存期显著延长，美国食品药品监督管理局于2018年2月14日批准阿帕鲁胺用于非转移性去势抵抗性前列腺癌患者。SPARTAN试验评估了1207例非转移性去势抵抗性前列腺癌患者，这些患者按2:1随机分组，分别接受阿帕鲁胺或安慰剂联合雄激素剥夺治疗。接受阿帕鲁胺治疗的患者在统计学上无转移生存期显著更长（40.5个月对16.2个月，风险比0.28（95%置信区间=0.23-0.35）；P<0.0001），这是主要疗效结果。据报道，与安慰剂相比，阿帕鲁胺治疗时皮疹、甲状腺功能减退和骨折的发生率更高。基于这些结果，阿帕鲁胺被认为是治疗非转移性去势抵抗性前列腺癌患者的一种安全有效的治疗选择。目前正在进行临床试验以扩大其在转移性疾病中的适应证，并确定阿帕鲁胺在前列腺癌治疗中的其他作用，如在去势敏感性转移性疾病中。
