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2015泌尿生殖系统肿瘤研讨会（ASCO GU）于2月26日至28日在美国奥兰多举行。在本次会议上展出的一项研究，在转移性去势抵抗性前列腺癌患者中，探索了雄激素受体V7（AR-V7）的存在与紫杉烷类耐药之间的相关性（摘要号 138）。医脉通对此进行了报道。
美国约翰•霍普金斯大学西德尼•基梅尔肿瘤综合中心肿瘤和泌尿学Emmanuel S. Antonarakis助理教授及其同事已证实循环肿瘤细胞（CTCs）中的雄激素受体V7（AR-V7）的存在与用恩杂鲁胺（Xtandi；Medivation；Astellas）和醋酸阿比特龙（Zytiga，Janssen）进行激素治疗的耐药有关。AR-V7是一种雄激素受体的缩减形式。研究人员试图确定循环肿瘤细胞中的 AR-V7是否也与紫杉烷类化疗耐药有关。
Emmanuel S. Antonarakis
他们分析了37例以多西他赛或cabazitaxel（jevtana，Sanofi-Aventis）为初始化疗的转移性去势抵抗性前列腺癌患者。
研究人员在17例（45.9%）患者的循环肿瘤细胞中检测到了AR-V7。
将紫杉烷醇化疗是否产生PSA应答作为研究的主要终点。41% 的AR-V7阳性疾病的男性产生了PSA应答，AR-V7阴性疾病的男性有65%产生了PSA应答。无统计学显著差异。
研究人员观察到， AR-V7阳性疾病与AR-V7阴性疾病男性在PFS（5.1个月和6.9个月；HR = 2.65）及中位PSA PFS（4.5个月和6.2个月；HR = 1.72）方面没有显著差异。
Antonarakis及其同事将这些数据与从AR-V7先前的研究结果进行比较，先前的数据包括62名接受恩杂鲁胺或阿比特龙治疗的男性。
在这两个AR-V7阳性的男性队列中，更大比例的接受紫杉烷类化疗的患者取得了PSA应答（41% vs 0%；P˂ .001）。那些经紫杉烷类化疗的男性，与接受激素治疗的男性相比，也表现出了显著较长的中位PSA PFS（HR = 0.19）和中位PFS（HR = 0.21）。
然而，AR-V7阴性疾病的男性对激素治疗或紫杉烷类化疗的应答相似。
“AR-V7可能会作为转移性去势抵抗性前列腺癌男性试图进行紫杉烷类或恩杂鲁胺和阿比特龙治疗的选择性标记物。Antonarakis在一个新闻发布会上说：“我认为，这种检测对有阳性结果的患者效用更大。在这些患者中，我们的数据表明，紫杉烷似乎稍微比恩杂鲁胺或阿比特龙治疗更有效。”
结果表明，两种治疗方法在AR-V7阴性的患者同样有效，Antonarakis说。
Alexandra Todak 指出，“因此，我认为阴性结果没有阳性结果那样有用。”他说。“不过，在该数据应用到临床之前，我们需要至少通过一个多中心临床试验来前瞻性的验证这一发现。”
医脉通编译自：AR-V7 status not associated with taxane chemotherapy resistance in advanced prostate cancer, Healio, February 24, 2015
摘要原文
Background: AR-V7 is a truncated form of AR that lacks the ligand-binding domain but remains constitutively active. We previously showed that detection of AR-V7 from circulating tumor cells (CTCs) in men with mCRPC was associated with primary resistance to enzalutamide and abiraterone. Here, we hypothesized that AR-V7[+] patients would retain sensitivity to taxane chemotherapy.
Methods: We used a qRT-PCR assay to interrogate CTCs for AR-V7 mRNA in prospectively enrolled patients with mCRPC starting docetaxel or cabazitaxel. We sought associations between AR-V7 status and PSA response rates (the primary endpoint), PSA progression-free survival (PSA-PFS), and clinical/radiographic progression-free survival (PFS). Multivariable regressions were performed to determine the independent effect of AR-V7 status on clinical outcomes. 36 taxane-treated men were required to produce a 2-sided 95% CI for the difference in PSA response rates (between AR-V7[+] and AR-V7[–] men) with an upper bound of 60%, assuming that 30% of men would be AR-V7[+].
Results: 37 taxane-treated patients were enrolled, and 17 (45.9%) had detectable AR-V7 in CTCs. PSA responses were achieved in both AR-V7[+] and AR-V7[–] men (41% vs 65%, P=0.19). Median PSA-PFS was comparable in AR-V7[+] and AR-V7[–] men (4.5 vs 6.2 mo, HR 1.72, P=0.32). Likewise, median PFS was comparable in AR-V7[+] and AR-V7[–] men (5.1 vs 6.9 mo, HR 2.65, P=0.11). After incorporating data from our prior study in 62 abi/enza-treated patients, it was observed that clinical outcomes in AR-V7[+] men were superior with taxanes than with abi/enza, while outcomes did not differ by treatment type in AR-V7[–] men. For example, in AR-V7[+] men, PSA responses were higher in taxane-treated versus abi/enza-treated men (41% vs 0%, P<0.001), and median PSA-PFS and PFS were longer in taxane-treated men (HR for PSA-PFS = 0.19, P=0.001; HR for PFS = 0.21, P=0.003).
Conclusions: Detection of AR-V7 in CTCs from men with mCRPC is not associated with primary resistance to taxane chemotherapy, and such patients may retain sensitivity to taxanes. Further, in AR-V7[+] men, taxanes appear to be more efficacious than abi/enza. AR-V7 may represent a treatment-selection marker in mCRPC.
