A randomized phase IIa study of quantified bone scan response in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 dichloride alone or in combination with abiraterone acetate/prednisone or enzalutamide.
A randomized phase IIa study of quantified bone scan response in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 dichloride alone or in combination with abiraterone acetate/prednisone or enzalutamide.
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DOI：
10.1016/j.esmoop.2021.100082
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发表时间：
2021-04
期刊：
影响因子：
7.3
通讯作者：
Sartor O
中科院分区：
文献类型：
--
作者：
Petrylak DP;Vaishampayan UN;Patel KR;Higano CS;Albany C;Dawson NA;Mehlhaff BA;Quinn DI;Nordquist LT;Wagner VJ;Siegel J;Trandafir L;Sartor O
在转移性去势抵抗性前列腺癌 (mCRPC) 中，使用 Technetium-99m 评估治疗反应和骨病变受到图像分辨率和主观性的限制。我们评估了骨扫描病灶面积 (BSLA)，这是对单独接受镭 223 或与雄激素受体途径抑制剂（阿比特龙/泼尼松或恩杂鲁胺）联合治疗的 mCRPC 患者的反应进行定量成像评估。这项随机、非比较性 IIa 期三臂试验 (NCT02034552) 评估了接受镭 223 联合/不联合阿比特龙/泼尼松或恩杂鲁胺治疗的 mCRPC 和骨转移男性中基于锝-99m 的 BSLA 反应率 (RR)、安全性、放射学无进展生存期 (rPFS) 和首次出现症状性骨骼事件 (SSE) 的时间。主要终点是第 24 周 BSLA RR。总体而言，63 名患者接受了治疗（阿比特龙/泼尼松联合疗法，n = 22；恩杂鲁胺联合疗法，n = 22；镭 223 单药疗法，n = 19）。中位治疗持续时间（任何研究治疗的第一剂到最后一剂）分别为 12 个月（阿比特龙/泼尼松组合）、10 个月（恩杂鲁胺组合）和 3 个月（镭 223 单一疗法）。第 24 周 BSLA RR 为 58% [80% 置信区间 (CI) 41% 至 74%；单侧 P < 0.0001； 11/19 名患者]使用阿比特龙/泼尼松联合治疗，50%（32% 至 68%；单侧 P < 0.0001；8/16 患者）使用恩杂鲁胺联合治疗，22%（10% 至 40%；单侧 P = 0.0109；4/18 患者）接受镭 223 单药治疗。联合治疗组的中位 rPFS 无法评估，单药治疗的中位 rPFS 为 4 个月（80% CI 4 至 12）。 32% 的患者报告有 SSE；首次 SSE 的中位时间无法估计。疲劳和背痛是最常报告的治疗引起的不良事件（TEAE）；接受联合治疗的患者比单一治疗的患者有更多的 TEAE。据报道，接受阿比特龙/泼尼松治疗的患者有 18% 发生骨折，接受恩杂鲁胺治疗的患者有 32%，接受镭 223 单一治疗的患者有 11%。基线时服用骨保健药物的患者与未服用骨保健药物的患者相比，骨折率较低。 Technetium-99m 成像 BSLA 可以对单独使用镭 223 或与阿比特龙/泼尼松或恩杂鲁胺联合治疗的 mCRPC 和骨转移患者提供客观、可量化的同位素摄取变化和潜在治疗反应评估。在这一大部分未接受过治疗的人群中，镭 223 单一疗法与联合疗法相比，BSLA RR 在数值上较低，表明作为一线治疗的作用有限。镭 223 的使用应遵循循证治疗指南和许可的适应症。 Radium-223 是一种针对骨主导型转移性去势抵抗性前列腺癌的靶向 α 疗法。使用 Technetium-99m 评估骨病变和治疗反应受到图像分辨率和主观性的限制。我们使用骨扫描病变区域 (BSLA) 的计算机辅助检测 (CAD) 来评估镭 223 ± 阿比特龙/恩杂鲁胺。初步评估显示，基于 CAD 的 BSLA 对镭 223 ± 阿比特龙/恩杂鲁胺治疗有积极反应。镭 223 的使用应遵循循证治疗指南和许可的适应症。
In metastatic castration-resistant prostate cancer (mCRPC), assessing treatment response and bone lesions with technetium-99m is limited by image resolution and subjectivity. We evaluated bone scan lesion area (BSLA), a quantitative imaging assessment of response in patients with mCRPC receiving radium-223 alone or in combination with androgen receptor pathway inhibitors (abiraterone/prednisone or enzalutamide). This randomized, non-comparative phase IIa three-arm trial (NCT02034552) evaluated technetium-99m-based BSLA response rate (RR), safety, radiologic progression-free survival (rPFS), and time to first symptomatic skeletal event (SSE) in men with mCRPC and bone metastases receiving radium-223 with/without abiraterone/prednisone or enzalutamide. The primary endpoint was week 24 BSLA RR. Overall, 63 patients received treatment (abiraterone/prednisone combination, n = 22; enzalutamide combination, n = 22; radium-223 monotherapy, n = 19). Median treatment duration (first to last dose of any study treatment) was 12 months (abiraterone/prednisone combination), 10 months (enzalutamide combination), and 3 months (radium-223 monotherapy). Week 24 BSLA RR was 58% [80% confidence interval (CI) 41% to 74%; one-sided P < 0.0001; 11/19 patients] with abiraterone/prednisone combination, 50% (32% to 68%; one-sided P < 0.0001; 8/16 patients) with enzalutamide combination, and 22% (10% to 40%; one-sided P = 0.0109; 4/18 patients) with radium-223 monotherapy. Median rPFS was not evaluable for combination arms and 4 months (80% CI 4 to 12) for monotherapy. SSEs were reported in 32% of patients; median time to first SSE was not estimable. Fatigue and back pain were the most commonly reported treatment-emergent adverse events (TEAEs); more patients receiving combination therapy than monotherapy had TEAEs. Fractures were reported in 18% receiving abiraterone/prednisone, 32% receiving enzalutamide, and 11% receiving radium-223 monotherapy. Fracture rates were lower in patients taking bone health agents versus not taking bone health agents at baseline. Technetium-99m imaging BSLA may offer objective, quantifiable assessment of isotope uptake changes, and potentially treatment response, in patients with mCRPC and bone metastases treated with radium-223 alone or in combination with abiraterone/prednisone or enzalutamide. In this largely treatment-naive population, BSLA RR was numerically lower with radium-223 monotherapy versus combination therapy, indicating a limited role as first-line treatment. Use of radium-223 should follow evidence-based treatment guidelines and the licensed indication. Radium-223 is a targeted alpha therapy for bone-dominant metastatic castration-resistant prostate cancer. Assessing bone lesions and treatment response with technetium-99m is limited by image resolution and subjectivity. We used computer-aided detection (CAD) of bone scan lesion area (BSLA) to assess radium-223 ± abiraterone/enzalutamide. On preliminary assessment, CAD-based BSLA demonstrated positive response to radium-223 ± abiraterone/enzalutamide therapy. Use of radium-223 should follow evidence-based treatment guidelines and the licensed indication.
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