Duke Cancer Institute Center for Prostate & Urologic Cancers, Durham, North Carolina.
Carolina Urologic Research Center, Myrtle Beach, South Carolina.
J Urol. 2021 May;205(5):1361-1371. doi: 10.1097/JU.0000000000001568. Epub 2020 Dec 28.
Enzalutamide plus androgen deprivation therapy has previously been shown to improve clinical outcomes in men with metastatic hormone-sensitive prostate cancer (ARCHES; NCT02677896). Here, we assessed if and how the pattern of metastatic spread impacts efficacy of enzalutamide plus androgen deprivation therapy in men enrolled in ARCHES.
Men with metastatic hormone-sensitive prostate cancer were randomized 1:1 to enzalutamide (160 mg/day) plus androgen deprivation therapy or placebo plus androgen deprivation therapy, stratified by disease volume and prior docetaxel treatment. The primary end point was radiographic progression-free survival. Secondary end points included time to prostate specific antigen progression, initiation of new antineoplastic therapy, first symptomatic skeletal event and castration resistance. Post hoc analyses were performed by pattern of metastatic spread based on study entry imaging.
Of the overall population with metastases identified at enrollment (1,146), the largest patient subgroups were those with bone metastases only (513) and those with bone plus lymph node metastases (351); there were fewer men with lymph node metastases only (154) and men with visceral±bone or lymph node metastases (128). Enzalutamide plus androgen deprivation therapy reduced the risk of radiographic progression vs placebo plus androgen deprivation therapy in men with bone metastases only (HR 0.33) and bone plus lymph node metastases (HR 0.31). Similar improvements in secondary end points were also observed in these subgroups.
These findings indicate that treatment with enzalutamide plus androgen deprivation therapy provides improvements in men with bone and/or lymph node metastases but may be less effective in men with visceral patterns of spread.
先前的研究表明，恩扎卢胺联合雄激素剥夺疗法可改善转移性去势敏感型前列腺癌患者的临床结局（ARCHES；NCT02677896）。在此，我们评估了转移性扩散模式是否以及如何影响 ARCHES 入组患者中恩扎卢胺联合雄激素剥夺疗法的疗效。
将转移性去势敏感型前列腺癌患者按疾病体积和既往多西他赛治疗情况以 1:1 的比例随机分为恩扎卢胺（160mg/天）联合雄激素剥夺疗法组或安慰剂联合雄激素剥夺疗法组。主要终点为影像学无进展生存期。次要终点包括前列腺特异抗原进展时间、新抗肿瘤治疗的开始时间、首次有症状的骨骼事件和去势抵抗。根据研究入组时的影像学检查结果，按转移性扩散模式进行了事后分析。
在所有入组时发现转移的患者（1146 例）中，最大的患者亚组为仅骨转移（513 例）和骨加淋巴结转移（351 例）；仅有淋巴结转移的患者较少（154 例），仅有内脏±骨或淋巴结转移的患者更少（128 例）。与安慰剂联合雄激素剥夺疗法相比，恩扎卢胺联合雄激素剥夺疗法降低了仅骨转移（HR 0.33）和骨加淋巴结转移（HR 0.31）患者的影像学进展风险。在这些亚组中，次要终点也观察到了类似的改善。
这些发现表明，恩扎卢胺联合雄激素剥夺疗法治疗可改善骨和/或淋巴结转移患者的预后，但对内脏转移模式患者的疗效可能较低。
