Royal Marsden Hospital, Sutton, London, UK.
Cancer Treatment Centers of America, Tulsa, OK, USA.
Eur Urol. 2016 Nov;70(5):875-883. doi: 10.1016/j.eururo.2016.06.002. Epub 2016 Jun 22.
The phase 3 ALSYMPCA trial enrolled metastatic castration-resistant prostate cancer patients with or without baseline opioid use.
To assess the efficacy and safety of radium-223 dichloride (radium-223) versus placebo in ALSYMPCA patients by baseline opioid use.
DESIGN, SETTING, AND PARTICIPANTS: Nine hundred and twenty one patients enrolled at 136 centers globally.
Radium-223 (50 kBq/kg, intravenous injection) every 4 wk for six cycles or matching placebo, each plus best standard of care.
Primary endpoint (overall survival [OS]), main secondary efficacy endpoints, and safety were evaluated by baseline opioid use. Additional analyses included time to first opioid use, time to first external beam radiation therapy for bone pain, and safety of concomitant external beam radiation therapy.
At baseline, 408 (44%) patients had no pain and no analgesic use or mild pain with nonopioid therapy (World Health Organization ladder pain score 0-1 [nonopioid subgroup]), and 513 (56%) had moderate pain with occasional opioids or severe pain with regular daily opioids (World Health Organization ladder pain score 2-3 [opioid subgroup]). Radium-223 significantly prolonged OS versus placebo in nonopioid (hazard ratio [HR]=0.70; 95% confidence interval [CI]: 0.52-0.93; p=0.013) and opioid (HR=0.68; 95% CI: 0.54-0.86; p=0.001) subgroups, and significantly reduced risk of symptomatic skeletal events versus placebo, regardless of baseline opioid use (nonopioid subgroup: HR=0.56, 95% CI: 0.39-0.82, p=0.002; opioid subgroup: HR=0.72, 95% CI: 0.53-0.98, p=0.038). Time to first opioid use for bone pain was significantly delayed with radium-223 versus placebo (HR=0.62, 95% CI: 0.46-0.85, p=0.002). Adverse event incidences were similar between opioid subgroups.
Radium-223 versus placebo significantly prolonged OS and reduced symptomatic skeletal event risk with a favorable safety profile in castration-resistant prostate cancer patients with symptomatic bone metastases, regardless of baseline opioid use.
In this ALSYMPCA opioid subgroup analysis, baseline symptom levels did not appear to impact radium-223 dichloride efficacy or safety.
在 3 期 ALSYMPCA 试验中，招募了有或没有基线阿片类药物使用的转移性去势抵抗性前列腺癌患者。
通过基线阿片类药物使用评估镭-223 二氯化物（镭-223）与安慰剂在 ALSYMPCA 患者中的疗效和安全性。
设计、地点和参与者：全球 136 个中心的 921 名患者入组。
镭-223（50 kBq/kg，静脉注射）每 4 周 1 次，共 6 个周期，或匹配安慰剂，均加最佳标准治疗。
主要终点（总生存期 [OS]）、主要次要疗效终点和安全性根据基线阿片类药物使用情况进行评估。其他分析包括首次使用阿片类药物的时间、首次使用外部束放射疗法治疗骨痛的时间以及同时使用外部束放射疗法的安全性。
基线时，408 名（44%）患者无疼痛且无镇痛药物或轻度疼痛（世界卫生组织疼痛评分 0-1 [非阿片类药物亚组]），513 名（56%）患者有中度疼痛且偶尔使用阿片类药物或有规律每日使用阿片类药物的重度疼痛（世界卫生组织疼痛评分 2-3 [阿片类药物亚组]）。镭-223 与安慰剂相比，在非阿片类药物（风险比 [HR]=0.70；95%置信区间 [CI]：0.52-0.93；p=0.013）和阿片类药物（HR=0.68；95% CI：0.54-0.86；p=0.001）亚组中显著延长了 OS，并且无论基线阿片类药物使用情况如何，均显著降低了与安慰剂相比的症状性骨骼事件风险（非阿片类药物亚组：HR=0.56，95% CI：0.39-0.82，p=0.002；阿片类药物亚组：HR=0.72，95% CI：0.53-0.98，p=0.038）。与安慰剂相比，首次使用阿片类药物治疗骨痛的时间显著延迟（HR=0.62，95% CI：0.46-0.85，p=0.002）。阿片类药物亚组的不良事件发生率相似。
在有症状性骨转移的去势抵抗性前列腺癌患者中，镭-223 与安慰剂相比，无论基线阿片类药物使用情况如何，均显著延长 OS 并降低了症状性骨骼事件风险，且安全性良好。
在这项 ALSYMPCA 阿片类药物亚组分析中，基线症状水平似乎并未影响镭-223 二氯化物的疗效或安全性。
