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雄激素受体阳性唾液腺癌患者恩杂鲁胺的 II 期研究(Alliance A091404)。

Phase II Study of Enzalutamide for Patients With Androgen Receptor-Positive Salivary Gland Cancers (Alliance A091404).

机构信息

Memorial Sloan Kettering Cancer Center, New York, NY.

Weill Cornell Medical College, New York, NY.

出版信息

J Clin Oncol. 2022 Dec 20;40(36):4240-4249. doi: 10.1200/JCO.22.00229. Epub 2022 Jul 22.

DOI:10.1200/JCO.22.00229
PMID:35867947
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9916043/
Abstract

PURPOSE

The androgen receptor (AR) is expressed (+) in a subset of salivary gland cancers (SGCs). This phase II trial evaluated the efficacy of the antiandrogen enzalutamide in AR+ SGC.

METHODS

Patients with locally advanced/unresectable or metastatic AR+ SGCs were enrolled. Enzalutamide (160 mg) was given orally once daily. The primary end point was the best overall response rate per RECIST v1.1 within eight cycles. Confirmed responses in ≥ 5 of 41 patients would be considered promising. Secondary end points were progression-free survival, overall survival, and safety.

RESULTS

Forty-six patients were enrolled; 30 (65.2%) received prior systemic therapy, including 13 (28.3%) with AR-targeted drugs. Of seven (15.2%) partial responses (PRs), only two (4.3%) were confirmed per protocol and counted toward the primary end point. Twenty-four patients (52.2%) had stable disease; 15 (32.6%) had progression of disease as best response. Twenty-six patients (56.5%) experienced tumor regression in target lesions; 18 (39.1%) had partial response/stable disease ≥ 6 months. Tumor regressions were observed in female patients (5 of 6 [83.3%]) and those who received prior AR- (6 of 13 [46.2%]) or human epidermal growth factor receptor 2-targeted therapies (5 of 8 [62.5%]). Three patients remained on treatment at data cutoff (duration, 32.2-49.8 months). The median progression-free survival was 5.6 months (95% CI, 3.7 to 7.5); the median overall survival was 17.0 months (95% CI, 11.8 to 30.0). The most common adverse events were fatigue, hypertension, hot flashes, and weight loss. Total and free testosterone levels increased by a mean of 61.2% and 48.8%, respectively, after enzalutamide.

CONCLUSION

Enzalutamide demonstrated limited activity in AR+ SGC, failing to meet protocol-defined success in part because of a lack of response durability. Strategies to enhance the efficacy of antiandrogen therapy are needed.

摘要

目的

雄激素受体 (AR) 在一部分唾液腺癌 (SGC) 中呈阳性表达。本 II 期试验评估了抗雄激素药物恩扎卢胺在 AR+SGC 中的疗效。

方法

入组局部晚期/不可切除或转移性 AR+SGC 患者。恩扎卢胺(160mg)每日口服一次。主要终点是根据 RECIST v1.1 标准,在 8 个周期内的最佳总体缓解率。如果 41 例患者中至少有 5 例出现确认缓解,将被认为是有希望的。次要终点是无进展生存期、总生存期和安全性。

结果

共入组 46 例患者;30 例(65.2%)患者接受了既往系统治疗,其中 13 例(28.3%)接受了 AR 靶向药物治疗。7 例(15.2%)部分缓解(PR)患者中,仅有 2 例(4.3%)符合方案要求并计入主要终点。24 例(52.2%)患者疾病稳定,15 例(32.6%)患者疾病进展为最佳缓解。26 例(56.5%)患者靶病灶肿瘤消退;18 例(39.1%)患者肿瘤缓解/疾病稳定≥6 个月。女性患者(6 例[83.3%])和接受 AR-(13 例中的 6 例[46.2%])或人表皮生长因子受体 2 靶向治疗(8 例中的 5 例[62.5%])的患者观察到肿瘤消退。截至数据截止时,有 3 例患者仍在接受治疗(持续时间为 32.2-49.8 个月)。中位无进展生存期为 5.6 个月(95%CI,3.7-7.5);中位总生存期为 17.0 个月(95%CI,11.8-30.0)。最常见的不良反应是疲劳、高血压、热潮红和体重减轻。恩扎卢胺治疗后总睾酮和游离睾酮水平分别平均升高 61.2%和 48.8%。

结论

恩扎卢胺在 AR+SGC 中显示出有限的活性,部分原因是缺乏持久反应,未能达到方案定义的成功。需要制定策略来增强抗雄激素治疗的疗效。

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