Abstract：
OBJECTIVE: Androgen receptor splice variant 7 (ARV-7) is a resistance mechanism to hormonal therapy in metastatic castrate-resistant prostate cancer (mCRPC). It has been associated with poor outcomes. On progression to castrate resistance, ARV-7 positivity has been identified in global populations at an incidence of 17.8%-28.8%. Here, we characterize the incidence of ARV-7 positivity in Asian patients with mCRPC in a prospective fashion and evaluate its implications on treatment outcomes.
METHODS: Patients with mCRPC from multiple centers in Southeast and East Asia were enrolled in a prospective manner before initiation of androgen receptor signaling inhibitors or docetaxel. ARV-7 status was evaluated at baseline with three commercially available assays: AdnaTest Prostate Cancer platform, Clearbridge method, and IBN method. Clinical outcomes at progression were assessed. The primary end point of this study was prevalence of ARV-7 positivity; secondary end points were incidence of ARV-7 positivity, prostate specific antigen (PSA) response rate, PSA progression-free survival (PFS), and overall survival (OS).
RESULTS: A total of 102 patients with a median age of 72 years at enrollment participated. Overall, an incidence of ARV-7 positivity of between 14.3% and 33.7% in Asian patients with mCRPC was demonstrated depending on the assay used. Patients found to have ARV-7 positivity at enrollment had a numerically worse PSA PFS compared with ARV-7 negative patients.
CONCLUSIONS: In this study, the incidence of ARV-7 positivity in Asian patients with mCRPC was shown to be similar to the global population. Patients with ARV-7 positivity appear to have more aggressive disease with numerically worse PSA PFS and OS. Further prospective studies are needed to fully characterize the relationship that ARV-7 positivity has on prognosis of Asian patients with mCRPC.
METHODS: Patients with mCRPC from multiple centers in Southeast and East Asia were enrolled in a prospective manner before initiation of androgen receptor signaling inhibitors or docetaxel. ARV-7 status was evaluated at baseline with three commercially available assays: AdnaTest Prostate Cancer platform, Clearbridge method, and IBN method. Clinical outcomes at progression were assessed. The primary end point of this study was prevalence of ARV-7 positivity; secondary end points were incidence of ARV-7 positivity, prostate specific antigen (PSA) response rate, PSA progression-free survival (PFS), and overall survival (OS).
RESULTS: A total of 102 patients with a median age of 72 years at enrollment participated. Overall, an incidence of ARV-7 positivity of between 14.3% and 33.7% in Asian patients with mCRPC was demonstrated depending on the assay used. Patients found to have ARV-7 positivity at enrollment had a numerically worse PSA PFS compared with ARV-7 negative patients.
CONCLUSIONS: In this study, the incidence of ARV-7 positivity in Asian patients with mCRPC was shown to be similar to the global population. Patients with ARV-7 positivity appear to have more aggressive disease with numerically worse PSA PFS and OS. Further prospective studies are needed to fully characterize the relationship that ARV-7 positivity has on prognosis of Asian patients with mCRPC.
摘要：
目的：雄激素受体剪接变体7（ARV-7）是转移性去势抵抗性前列腺癌（mCRPC）激素治疗的一种耐药机制。这与糟糕的结果有关。在进展为去势抗性时，在全球人群中，ARV-7阳性发生率为17.8%-28.8%。这里,我们前瞻性地描述了亚裔mCRPC患者ARV-7阳性发生率,并评估了其对治疗结局的影响.
方法：在启动雄激素受体信号抑制剂或多西他赛之前，前瞻性招募了来自东南亚和东亚多个中心的mCRPC患者。ARV-7状态在基线时使用三种市售检测方法进行评估：AdnaTest前列腺癌平台，Clearbridge方法,和IBN方法。评估进展时的临床结果。这项研究的主要终点是ARV-7阳性的患病率；次要终点是ARV-7阳性的发生率。前列腺特异性抗原（PSA）反应率，PSA无进展生存期（PFS），总生存率（OS）。
结果：共有102名患者参加，中位年龄为72岁。总的来说,根据所使用的检测方法,在亚裔mCRPC患者中,ARV-7阳性发生率为14.3%~33.7%.与ARV-7阴性患者相比，在招募时发现具有ARV-7阳性的患者的PSAPFS在数字上较差。
结论：在这项研究中，结果显示,亚洲mCRPC患者的ARV-7阳性发生率与全球人群相似.ARV-7阳性的患者似乎患有更具侵袭性的疾病，PSAPFS和OS在数字上较差。需要进一步的前瞻性研究来充分表征ARV-7阳性与mCRPC亚洲患者预后的关系。
方法：在启动雄激素受体信号抑制剂或多西他赛之前，前瞻性招募了来自东南亚和东亚多个中心的mCRPC患者。ARV-7状态在基线时使用三种市售检测方法进行评估：AdnaTest前列腺癌平台，Clearbridge方法,和IBN方法。评估进展时的临床结果。这项研究的主要终点是ARV-7阳性的患病率；次要终点是ARV-7阳性的发生率。前列腺特异性抗原（PSA）反应率，PSA无进展生存期（PFS），总生存率（OS）。
结果：共有102名患者参加，中位年龄为72岁。总的来说,根据所使用的检测方法,在亚裔mCRPC患者中,ARV-7阳性发生率为14.3%~33.7%.与ARV-7阴性患者相比，在招募时发现具有ARV-7阳性的患者的PSAPFS在数字上较差。
结论：在这项研究中，结果显示,亚洲mCRPC患者的ARV-7阳性发生率与全球人群相似.ARV-7阳性的患者似乎患有更具侵袭性的疾病，PSAPFS和OS在数字上较差。需要进一步的前瞻性研究来充分表征ARV-7阳性与mCRPC亚洲患者预后的关系。
