Maughan Benjamin L, Liu Yanfang, Mundle Suneel, Wang Xiayi, Nematian-Samani Mehregan, Karsh Lawrence I
Huntsman Cancer Institute, University of Utah, 2000 Cir of Hope Dr, Salt Lake City, UT, 84112, USA.
Department of Global Real-World Evidence, Janssen Pharmaceuticals LLC, 1000 U.S. Route 202, Raritan, NJ, 08869, USA.
Prostate Cancer Prostatic Dis. 2024 Dec 20. doi: 10.1038/s41391-024-00929-6.
Androgen receptor pathway inhibitors (apalutamide [APA], enzalutamide [ENZ], abiraterone acetate plus prednisone [AAP]) combined with androgen-deprivation therapy (ADT) are effective life-prolonging treatment options for metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the impact of upfront therapy for mHSPC on outcomes in real-world clinical practice in the United States.
This retrospective, observational cohort study used electronic healthcare records from the ConcertAI RWD 360 Prostate Cancer Dataset. All patients with newly diagnosed mHSPC from January 2018 to June 2023 were enrolled and followed-up until death, end of follow-up, or January 2024, whichever occurred first. Kaplan-Meier methods were used to estimate overall survival (OS), time to PSA50/PSA90 (50%/90% decline in PSA from baseline, respectively), time to undetectable PSA ( ≤ 0.2 ng/ml), and time to castration resistance (TTCR). Adjusted hazard ratios (aHR) were estimated using inverse probability of treatment weighted multivariate Cox proportional models adjusted for age, comorbidities, BMI, and baseline PSA.
4937 patients with mHSPC were included in the analysis: 315 received upfront APA + ADT, 1181 ENZ + ADT, 1760 AAP + ADT, 432 docetaxel (DTX) + ADT, and 1249 ADT alone. Percentages of patients reaching PSA50, PSA90, and undetectable PSA at 3 months were significantly higher for APA + ADT (70%/49%/44%, respectively) compared to ENZ + ADT (60%/38%/32%), AAP + ADT (59%/37%/33%) and ADT alone (32%/15%/32%). OS and TTCR were also significantly longer for APA + ADT (66%/77% respectively at 24 months) vs ENZ + ADT (55%/63%) AAP + ADT (59%/67%) and ADT alone (54%/57%). Starting treatment with APA + ADT was associated with a significantly reduced risk of death compared with ENZ + ADT (aHR, 95%CI) (0.66, 0.51-0.87), AAP + ADT (0.72, 0.55-0.94), and ADT alone (0.64, 0.49-0.84).
Numerous patients were not treated with intensified therapies despite their increased effectiveness. First-line APA + ADT in mHSPC was associated with statistically significantly longer OS, longer TTCR, and faster and deeper PSA responses than other life-prolonging treatments in real-world clinical practice in the US.
雄激素受体通路抑制剂（阿帕他胺[APA]、恩杂鲁胺[ENZ]、醋酸阿比特龙加泼尼松[AAP]）联合雄激素剥夺治疗（ADT）是转移性激素敏感性前列腺癌（mHSPC）有效的延长生命的治疗选择。我们评估了美国真实世界临床实践中mHSPC初始治疗对预后的影响。
这项回顾性观察性队列研究使用了ConcertAI RWD 360前列腺癌数据集的电子医疗记录。纳入所有2018年1月至2023年6月新诊断的mHSPC患者，并随访至死亡、随访结束或2024年1月，以先发生者为准。采用Kaplan-Meier方法估计总生存期（OS）、达到PSA50/PSA90的时间（分别为PSA从基线下降50%/90%）、PSA不可检测的时间（≤0.2 ng/ml）以及去势抵抗时间（TTCR）。使用逆概率治疗加权多变量Cox比例模型估计调整后的风险比（aHR），该模型针对年龄、合并症、BMI和基线PSA进行了调整。
4937例mHSPC患者纳入分析：315例接受初始APA + ADT治疗，1181例接受ENZ + ADT治疗，1760例接受AAP + ADT治疗，432例接受多西他赛（DTX）+ ADT治疗，1249例仅接受ADT治疗。与ENZ + ADT（分别为60%/38%/32%）、AAP + ADT（59%/...
