BACKGROUND In Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial, radium-223 versus placebo prolonged overall survival with favorable safety in castration-resistant prostate cancer patients with symptomatic bone metastases. Long-term radium-223 monitoring underlies a comprehensive safety and risk/benefit assessment. OBJECTIVE To report updated ALSYMPCA safety, including long-term safety up to 3 yr after the first injection. DESIGN, SETTING, AND PARTICIPANTS Safety analyses from phase 3 randomized ALSYMPCA trial included patients receiving ≥1 study-drug injection (600 radium-223 and 301 placebo). Patients (405 radium-223 and 167 placebo) entered long-term safety follow-up starting 12 wk after the last study-drug injection, to 3 yr from the first injection. Forty-eight of 405 (12%) radium-223 and 12/167 (7%) placebo patients completed follow-up, with evaluations every 2 mo for 6 mo, then every 4 mo until 3 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS All adverse events (AEs) were collected until 12 wk after the last injection; subsequently, only treatment-related AEs were collected. Additional long-term safety was assessed by development of acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), aplastic anemia, and secondary malignancies. Data analysis used descriptive statistics. RESULTS AND LIMITATIONS During treatment to 12 wk following the last injection, 564/600 (94%) radium-223 and 292/301 (97%) placebo patients had treatment-emergent AEs (TEAEs). Myelosuppression incidence was low. Grade 3/4 hematologic TEAEs in radium-223 and placebo groups were anemia (13% vs 13%), neutropenia (2% vs 1%), and thrombocytopenia (7% vs 2%). Ninety-eight of 600 (16%) radium-223 and 68/301 (23%) placebo patients experienced grade 5 TEAEs. Long-term follow-up showed no AML, MDS, or new primary bone cancer; secondary non-treatment-related malignancies occurred in four radium-223 and three placebo patients. One radium-223 patient had aplastic anemia 16 mo after the last injection. No other cases were observed. Limitations include short (3-yr) follow-up. CONCLUSIONS Final long-term safety ALSYMPCA analysis shows that radium-223 remained well tolerated, with low myelosuppression incidence and no new safety concerns. PATIENT SUMMARY Updated Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial findings show that radium-223 remained well tolerated during treatment and up to 3 yr after each patient's first injection.

中文翻译：

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在有症状的前列腺癌试验中，来自 3 期随机 Alpharadin 的去势抵抗性前列腺癌和有症状的骨转移患者中二氯化镭 223 的三年安全性。

背景 在 Alpharadin 治疗症状性前列腺癌 (ALSYMPCA) 试验中，镭 223 与安慰剂相比，在有症状性骨转移的去势抵抗性前列腺癌患者中延长了总体生存期，并且具有良好的安全性。对镭 223 的长期监测是全面安全和风险/效益评估的基础。目的 报告更新的 ALSYMPCA 安全性，包括第一次注射后长达 3 年的长期安全性。设计、设置和参与者 3 期随机 ALSYMPCA 试验的安全性分析包括接受≥1 次研究药物注射（600 镭 223 和 301 安慰剂）的患者。患者（405 名镭 223 和 167 名安慰剂）从最后一次研究药物注射后 12 周开始进入长期安全性随访，到第一次注射后 3 年。405 名 (12%) 镭 223 和 12/167 (7%) 名安慰剂患者中的 48 名完成了随访，每 2 个月评估一次，持续 6 个月，然后每 4 个月评估一次，直到 3 年。结果测量和统计分析 所有不良事件 (AE) 均收集到最后一次注射后 12 周；随后，仅收集与治疗相关的 AE。通过急性髓性白血病 (AML)、骨髓增生异常综合征 (MDS)、再生障碍性贫血和继发性恶性肿瘤的发展评估了额外的长期安全性。数据分析使用描述性统计。结果和局限性 在最后一次注射后至 12 周的治疗期间，564/600 (94%) 镭 223 和 292/301 (97%) 安慰剂患者出现治疗出现的 AE (TEAE)。骨髓抑制发生率低。镭 223 组和安慰剂组的 3/4 级血液学 TEAE 为贫血（13% 对 13%），中性粒细胞减少症（2% 对 1%）和血小板减少症（7% 对 2%）。600 名 (16%) 镭 223 和 68/301 (23%) 名安慰剂患者中有 98 名经历了 5 级 TEAE。长期随访未发现 AML、MDS 或新的原发性骨癌；4 名镭 223 和 3 名安慰剂患者发生继发性非治疗相关恶性肿瘤。一名镭223患者在最后一次注射后16个月出现再生障碍性贫血。没有观察到其他病例。限制包括短期（3 年）随访。结论 最终的长期安全性 ALSYMPCA 分析表明，镭 223 的耐受性良好，骨髓抑制发生率低，没有新的安全问题。患者总结 更新的 Alpharadin 治疗症状性前列腺癌 (ALSYMPCA) 试验结果表明，镭 223 在治疗期间和每位患者首次注射后长达 3 年的耐受性良好。