Chesapeake Urology, Towson, MD.
Analysis Group, Inc., Montréal, QC, Canada.
Urol Oncol. 2023 May;41(5):253.e1-253.e9. doi: 10.1016/j.urolonc.2023.03.003. Epub 2023 Apr 13.
Deep prostate-specific antigen (PSA) response, defined as a ≥90% decline in PSA (PSA90), is an important early response indicator for achieving radiographic progression-free and overall survival in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with a next-generation androgen signaling inhibitor (ASI), such as apalutamide or enzalutamide. The objective of this study was to compare deep PSA response among patients with mCSPC newly initiated on apalutamide or enzalutamide.
Clinical data from 69 community urology practices in the United States were evaluated. Patients with mCSPC were classified into cohorts based on their first dispensation (index date) for apalutamide or enzalutamide and were followed until the earliest of treatment discontinuation, initiation of a new next-generation androgen receptor signaling inhibitor, end of clinical activity (including death), or end of data availability (03/05/2021). Inverse probability of treatment weights (IPTW) were used to reduce baseline confounding. PSA90 was defined as the earliest ≥90% PSA decline relative to baseline PSA. The proportion of patients achieving PSA90 and time to PSA90 were reported using weighted Kaplan-Meier analysis and weighted Cox proportional hazards models, respectively.
The apalutamide and enzalutamide cohorts comprised 186 and 165 patients, respectively. Patient characteristics were generally well balanced after IPTW. By 6 months, patients initiated on apalutamide had a 56% greater likelihood of attaining PSA90 than those initiated on enzalutamide (P = 0.014). This result remained significant through the end of the observation period. The median time to achieving PSA90 was 3.1 months with apalutamide and 5.2 months with enzalutamide.
This real-world study demonstrated that apalutamide initiation is associated with a significantly higher likelihood of achieving ≥90% reduction in PSA as compared to initiation of enzalutamide. Moreover, this deep PSA response was observed to occur earlier with apalutamide treatment than with enzalutamide.
深度前列腺特异性抗原（PSA）应答定义为 PSA 下降≥90%（PSA90），是接受下一代雄激素信号抑制剂（ASI）治疗的转移性去势敏感前列腺癌（mCSPC）患者实现影像学无进展和总生存的重要早期应答指标，此类 ASI 包括阿帕鲁胺或恩扎卢胺。本研究旨在比较新诊断为 mCSPC 的患者中，阿帕鲁胺和恩扎卢胺起始治疗后的深度 PSA 应答。
对美国 69 家社区泌尿科实践中的临床数据进行了评估。根据患者阿帕鲁胺或恩扎卢胺的首次配药（索引日期），将患者分为队列，并随访至治疗停止、开始新的下一代雄激素受体信号抑制剂、临床活动结束（包括死亡）或数据可用结束（2021 年 3 月 5 日）。采用逆概率治疗权重（IPTW）降低基线混杂。PSA90 定义为与基线 PSA 相比最早的 PSA 下降≥90%。使用加权 Kaplan-Meier 分析和加权 Cox 比例风险模型分别报告达到 PSA90 的患者比例和 PSA90 时间。
阿帕鲁胺和恩扎卢胺队列分别包含 186 例和 165 例患者。经 IPTW 后，患者特征基本均衡。在 6 个月时，起始阿帕鲁胺治疗的患者 PSA90 应答的可能性比起始恩扎卢胺治疗的患者高 56%（P=0.014）。这一结果在观察期结束时仍然显著。达到 PSA90 的中位时间为阿帕鲁胺 3.1 个月，恩扎卢胺为 5.2 个月。
这项真实世界研究表明，与恩扎卢胺相比，阿帕鲁胺起始治疗与 PSA 降低≥90%的可能性显著增加相关。此外，与恩扎卢胺相比，阿帕鲁胺治疗更早出现这种深度 PSA 应答。
