编者按：2026年美国临床肿瘤学会泌尿生殖系统肿瘤研讨会（ASCO GU 2026）已圆满落幕，会议期间多项前列腺癌领域重磅研究结果公布，为临床实践带来了高级别循证依据。其中，由欧洲癌症研究与治疗组织（EORTC）牵头开展的国际多中心、随机、开放标签III期EORTC 1333/PEACE-3试验，公布了其关键次要终点—最终总生存期（OS）的阳性结果，为伴骨转移的转移性去势抵抗性前列腺癌（mCRPC）治疗带来了里程碑式的革新。肿瘤瞭望-泌尿时讯特邀西班牙ParcTauli大学医院Enrique Gallardo教授进行深度专访，全面解读研究核心发现、临床实践启示、安全管理要点与未来探索方向。

 

Enrique Gallardo教授：EORTC 1333/PEACE-3是一项国际多中心、随机、开放的III期临床试验，旨在评估恩扎卢胺联合镭-223对比恩扎卢胺单药，用于一线治疗伴有骨转移的转移性去势抵抗性前列腺癌（mCRPC）患者的疗效与安全性。该研究共纳入446例无症状或轻度症状且存在骨转移（≥2处）的mCRPC患者。患者被随机分配至两组：联合治疗组接受镭-223（55 kBq/kg，每4周一次，共6个周期）联合恩扎卢胺（160 mg，每日一次口服）；单药组则仅接受恩扎卢胺（160 mg，每日一次口服）。研究的主要终点为影像学无进展生存期（rPFS）；关键次要终点包括总生存期（OS）、至后续治疗时间、疼痛进展时间、症状性骨骼事件发生率及安全性评估。

 

PEACE-3试验结果证实，恩扎卢胺联合镭-223治疗方案，可为伴骨转移的mCRPC患者带来影像学无进展生存期（rPFS）与OS的双重显著获益，这也是我在本次ASCO GU大会上重点汇报的核心内容。在研究主要终点rPFS方面，联合治疗组的风险比（HR）为0.71，相较于恩扎卢胺单药组，rPFS显著延长3个月，达到19.2个月；在OS这一肿瘤治疗疗效的金标准终点上，联合治疗组的HR为0.76，中位OS较单药组显著延长5.6个月，达到38.2个月，充分证实了该联合方案相较于单药治疗的明确生存优势与临床价值。

 

Oncology Frontier:Thank you，Prof.Gallardo，for accepting our interview.First，could you briefly share the key core findings of the PEACE-3 trial evaluating enzalutamide plus radium-223 in patients with mCRPC?

 

Prof.Enrique Gallardo:EORTC 1333/PEACE-3 is an international，multicenter，randomized，open-label phase III clinical trial designed to assess the efficacy and safety of enzalutamide combined with radium-223 versus enzalutamide monotherapy as first-line treatment for patients with mCRPC and bone metastases.A total of 446 patients with asymptomatic or minimally symptomatic mCRPC with≥2 bone metastases and no visceral involvement were enrolled in the study.Patients were randomly assigned to two groups:the combination group received radium-223(55 kBq/kg intravenously every 4 weeks for 6 cycles)plus enzalutamide(160 mg orally once daily)，while the monotherapy group received enzalutamide alone(160 mg orally once daily).The primary endpoint of the study was radiographic progression-free survival(rPFS);key secondary endpoints included overall survival(OS)，time to subsequent systemic therapy，time to pain progression，incidence of symptomatic skeletal events(SSEs)，and safety assessment.

 

The results of the PEACE-3 trial confirmed that the enzalutamide plus radium-223 regimen brings significant dual benefits in both rPFS and OS for patients with mCRPC and bone metastases，which is the core content I highlighted in my oral presentation at this ASCO GU symposium.For the primary endpoint of rPFS，the combination group achieved a significantly prolonged rPFS of 19.2 months，a 3-month extension compared with the enzalutamide monotherapy group，with a hazard ratio(HR)of 0.71.For OS，the gold standard endpoint for evaluating cancer treatment efficacy，the median OS was significantly prolonged by 5.6 months in the combination group，reaching 38.2 months versus 32.6 months in the monotherapy group，with an HR of 0.76.These findings fully demonstrate the clear survival advantage and clinical value of this combination regimen over monotherapy.

Enrique Gallardo教授：PEACE-3试验的入组人群覆盖范围广泛，涵盖了既往仅接受过单纯雄激素剥夺治疗（ADT）、或ADT联合多西他赛化疗的患者，同时也纳入了既往接受过阿比特龙治疗的患者。基于这一特征，我认为恩扎卢胺联合镭-223方案，可成为这类伴骨转移mCRPC患者的标准治疗选择之一。

 

尤其值得关注的是，对于既往接受过阿比特龙治疗后进展为去势抵抗性前列腺癌的患者，该联合方案同样展现出了显著的治疗潜力。该方案不仅给药方式便捷、临床可操作性强，更带来了兼具统计学显著性与明确临床意义的生存获益。因此我认为，该方案至少应被视为伴骨转移mCRPC患者的一线优质治疗选择；即便患者既往接受过雄激素受体通路抑制剂（ARPi）治疗，临床决策中也应充分考量该联合方案的应用价值。

 

Oncology Frontier:What impact do you think the positive final OS results of this study will have on the current treatment landscape and clinical practice of mCRPC?

 

Prof.Enrique Gallardo:The PEACE-3 trial enrolled a broad patient population，including those who had previously received only androgen deprivation therapy(ADT)，ADT plus docetaxel chemotherapy，and even those with prior abiraterone exposure.Based on this characteristic，I believe the enzalutamide plus radium-223 regimen can become one of the standard treatment options for these patients with mCRPC and bone metastases.

 

Of particular note，the combination regimen also showed significant therapeutic potential in patients who progressed to castration-resistant prostate cancer after prior abiraterone treatment.This regimen not only has a convenient administration route and strong clinical operability，but also delivers a survival benefit that is both statistically significant and clinically meaningful.Therefore，I believe this regimen should at least be regarded as a high-quality first-line treatment option for patients with mCRPC and bone metastases;even in patients with prior exposure to androgen receptor pathway inhibitors(ARPIs)，the value of this combination regimen should be fully considered in clinical decision-making.

 

Enrique Gallardo教授：临床应用的核心关注点，在于方案的安全性全程管理，尤其是患者的骨健康保护。

 

总体而言，联合治疗方案的不良事件发生率呈现轻微且可控的增加：≥3级治疗期间出现的不良事件（TEAE）在联合组中为69.3%，单药组为57.6%；药物相关≥3级不良事件（AE）在联合组中为28.9%，单药组为18.8%。其中尤为值得关注的是骨折风险的变化。自2018年3月试验方案修订后强制实施骨保护剂（双膦酸盐或地舒单抗）的预防性用药，恩扎卢胺联合镭-223治疗组中3/4级骨折发生率为5.5%，而恩扎卢胺单药组为1.3%。若不区分等级，总体骨折发生率在联合组中为24.3%，单药组为13.4%。联合组所观察到的骨折风险升高，在强制骨保护剂应用的基础上得到有效缓解。基于该安全性特征，临床采用该联合方案时，必须同步规范使用骨保护剂（如地舒单抗或双膦酸盐类药物），以最大限度降低骨折发生风险。值得注意的是，不仅在该联合治疗方案中，对于所有伴有骨转移的转移性去势抵抗性前列腺癌（mCRPC）患者，临床实践中均应系统性启动骨保护剂治疗，贯穿治疗全程，以保障患者的骨骼健康与治疗安全性。

 

Oncology Frontier:When applying this combination regimen in clinical practice，what are the core points that clinicians need to pay the most attention to?

 

Prof.Enrique Gallardo:The core focus of clinical application lies in the full-cycle safety management of the regimen，especially the protection of patients’bone health.

 

Overall，the combination regimen showed a mild and controllable increase in the incidence of adverse events:grade≥3 treatment-emergent adverse events(TEAEs)occurred in 69.3%of patients in the combination group versus 57.6%in the monotherapy group;drug-related grade≥3 adverse events(AEs)were reported in 28.9%of the combination group versus 18.8%of the monotherapy group.Among them，the change in fracture risk is particularly noteworthy.Following the protocol amendment in March 2018 that mandated prophylactic treatment with bone-protective agents(bisphosphonates or denosumab)，the incidence of grade 3/4 fractures was 5.5%in the enzalutamide plus radium-223 group versus 1.3%in the enzalutamide monotherapy group.The overall fracture incidence(regardless of grade)was 24.3%in the combination group versus 13.4%in the monotherapy group.The increased fracture risk observed in the combination group was effectively mitigated on the basis of mandatory bone-protective agent use.

 

Based on this safety profile，when adopting this combination regimen in clinical practice，it is mandatory to concurrently and standardly administer bone-protective agents(such as denosumab or bisphosphonates)to minimize the risk of fractures.Importantly，not only for this combination regimen，but for all patients with mCRPC and bone metastases，bone-protective agent therapy should be systematically initiated in clinical practice and continued throughout the treatment course to protect patients’bone health and treatment safety.

Enrique Gallardo教授：PEACE-3试验的亚组分析结果显示，几乎所有预设亚组的患者，均能从恩扎卢胺联合镭-223方案中获得一致的生存获益。因此，从意向性治疗（ITT）人群的整体结果来看，所有符合适应症的伴骨转移mCRPC患者，均应在临床中考虑该治疗方案。

 

当然，亚组分析中我们也观察到，年龄＞75岁的老年患者、既往接受过多西他赛化疗的患者，以及体能状态较差的患者，其获益程度相较于其他亚组略低。但需要说明的是，上述亚组的样本量相对有限，目前尚无法得出确定性的结论。总体而言，所有伴骨受累、无内脏转移的mCRPC患者，均应将该联合方案纳入临床治疗的核心考量范围。

 

Oncology Frontier:Based on the subgroup analysis results of the trial，which patient subgroup do you think can derive the maximum survival benefit from this combination regimen?

 

Prof.Enrique Gallardo:The subgroup analysis of the PEACE-3 trial showed that nearly all prespecified subgroups of patients derived consistent survival benefits from the enzalutamide plus radium-223 regimen.Therefore，from the overall results of the intention-to-treat(ITT)population，all eligible patients with mCRPC and bone metastases should be considered for this treatment regimen in clinical practice.

 

Of course，in the subgroup analysis，we observed that elderly patients aged>75 years，patients who had received prior docetaxel chemotherapy，and patients with poorer performance status had a slightly lower magnitude of benefit compared with other subgroups.However，it should be noted that the sample size of these subgroups is relatively limited，and no definitive conclusions can be drawn at present.Overall，all patients with mCRPC with bone-predominant disease and no visceral metastases should include this combination regimen in the core consideration of clinical treatment.

Enrique Gallardo教授：未来最核心的探索方向，是将该联合方案向疾病更早阶段推进，尤其是在转移性激素敏感性前列腺癌（mHSPC）患者中，开展临床试验验证该方案的疗效与安全性。

 

目前，所有能够为前列腺癌患者带来生存获益的治疗方案，均在向疾病更早线布局，但该联合方案在mHSPC人群中能否实现OS获益，仍有待进一步的循证医学证据验证。而在当下，我认为最核心的工作，是将PEACE-3试验证实有效的这一联合方案，切实落地到临床实践中，规范用药与安全管理，让更多mCRPC患者从治疗中获益。

 

Oncology Frontier:Looking ahead，what do you think are the next research plans or core exploration directions for the optimized application of these two agents in the treatment of prostate cancer?

 

Prof.Enrique Gallardo:The core exploration direction in the future is to advance this combination regimen to earlier disease stages，especially to conduct clinical trials to verify the efficacy and safety of this regimen in patients with metastatic hormone-sensitive prostate cancer(mHSPC).

 

At present，all treatment regimens that can bring survival benefits to prostate cancer patients are being deployed in earlier lines of the disease，but whether this combination regimen can achieve OS benefits in the mHSPC population still needs further validation from evidence-based medicine.For now，I believe the core priority is to effectively translate this effective combination regimen confirmed by the PEACE-3 trial into clinical practice，standardize drug administration and safety management，and allow more patients with mCRPC to benefit from the treatment.

 

Enrique Gallardo教授

西班牙ParcTauli大学医院