Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Prostate. 2021 May;81(7):390-397. doi: 10.1002/pros.24115. Epub 2021 Mar 11.
Real-world utilization and outcomes of combination therapy for men with metastatic castrate-resistant prostate cancer (mCRPC) are largely unknown. We evaluated the overall survival (OS) and skeletal-related events (SREs) among men who received radium-223 with or without concomitant abiraterone or enzalutamide in the Veterans Affairs (VA) Health System.
We reviewed charts of all mCRPC patients who received radium-223 in the VA from January 2013 to September 2017. We used Cox models to test the association between concomitant therapy versus radium-223 alone on OS and SRE. Sensitivity analyses were performed for concomitant use of denosumab/bisphosphonates.
Three hundred and eighteen patients treated with radium-223 were identified; 116/318 (37%) received concomitant abiraterone/enzalutamide. Two hundred and seventy-seven (87%) patients died during follow-up. Patients who received concomitant therapy were younger at radium-223 initiation (median age 68 vs. 70, p = .027) and had a longer follow-up (median 29.5 vs. 17.9 months, p = .030). There was no OS benefit for those on concomitant therapy (hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.67-1.12, p = .28). There was a trend for an increased SRE risk for patients on concomitant therapy (HR: 1.87, 95% CI: 0.96-3.61, p = .066), but this was not significant. When analyses were limited to men using bone heath agents, similar results were seen for OS (HR: 0.86, 95% CI 0.64-1.15, p = .30) and SRE (HR: 2.36, 95% CI: 0.94-5.94, p = .068).
Despite the common use of concomitant therapy in this real-world study, there was no difference in OS among mCRPC patients. A nonsignificant increased SRE risk was observed. Further work needs to evaluate the optimal sequence, timing, and safety of combination therapies.
转移性去势抵抗性前列腺癌（mCRPC）患者的联合治疗的实际应用和结果在很大程度上尚不清楚。我们评估了退伍军人事务部（VA）卫生系统中接受镭-223 联合或不联合阿比特龙或恩扎卢胺治疗的男性的总生存期（OS）和骨骼相关事件（SREs）。
我们回顾了 2013 年 1 月至 2017 年 9 月期间在 VA 接受镭-223 治疗的所有 mCRPC 患者的病历。我们使用 Cox 模型检验了联合治疗与单独使用镭-223 对 OS 和 SRE 的关联。对 denosumab/双磷酸盐的联合使用进行了敏感性分析。
共确定了 318 例接受镭-223 治疗的患者；116/318（37%）例接受了阿比特龙/恩扎卢胺联合治疗。277 例（87%）患者在随访期间死亡。接受联合治疗的患者在开始镭-223 治疗时年龄较小（中位年龄 68 岁 vs. 70 岁，p=0.027），随访时间较长（中位随访 29.5 个月 vs. 17.9 个月，p=0.030）。联合治疗组的 OS 无获益（风险比 [HR]：0.87，95%置信区间 [CI]：0.67-1.12，p=0.28）。联合治疗组 SRE 风险有增加的趋势（HR：1.87，95%CI：0.96-3.61，p=0.066），但无统计学意义。当分析仅限于使用骨骼健康药物的男性时，OS（HR：0.86，95%CI：0.64-1.15，p=0.30）和 SRE（HR：2.36，95%CI：0.94-5.94，p=0.068）的结果相似。
尽管在这项真实世界研究中联合治疗的使用很常见，但 mCRPC 患者的 OS 没有差异。观察到 SRE 风险略有增加。需要进一步的工作来评估联合治疗的最佳顺序、时机和安全性。
