Dalla Volta Alberto, Valcamonico Francesca, Zivi Andrea, Procopio Giuseppe, Sepe Pierangela, Del Conte Gianluca, Di Meo Nunzia, Foti Silvia, Zamboni Stefania, Messina Caterina, Lucchini Eleonora, Rizzi Anna, Ravanelli Marco, Calza Stefano, Zacchi Francesca, Ciccone Giovannino, Suardi Nazareno, Maroldi Roberto, Farina Davide, Berruti Alfredo
Unit of Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, ASST Spedali Civili di Brescia, University of Brescia, Brescia, Italy.
Division of Oncology, Verona University and Hospital Trust (AOUI), Verona, Italy.
Prostate Cancer Prostatic Dis. 2025 May 3. doi: 10.1038/s41391-025-00975-8.
Zoledronic acid (ZA) in combination with androgen deprivation therapy (ADT) has never proved additional activity in patients with advanced prostate cancer. However, conventional imaging is poorly reliable in monitoring disease response of metastatic bone lesions.
BonEnza is a randomized phase II multicenter clinical trial designed to compare activity of ADT plus Enzalutamide (E) plus/minus ZA in term of bone response rate by Whole-Body Diffusion-Weighted Magnetic Resonance Imaging (WB-DW-MRI). From February 2018 to June 2021, 126 patients with metastatic hormone-sensitive prostate cancer (mHSPC) and bone metastasis at bone scan were enrolled. Patients were randomized in a 1:1 to receive E 160 mg OD orally alone (E arm) or in combination with ZA 4 mg intravenously every 4 weeks (EZ arm). Primary endpoint of the study was overall response rate (ORR) in bone metastases, secondary endpoints were ORR with conventional imaging, progression free survival (PFS) and overall survival (OS). A logistic model was used to evaluate the association between treatment arm and ORR.
After a median follow-up of 31.9 months, according to an intent to treat analysis, the ORR was superimposable in both arms: 69.8% (95% Confidence Interval [CI]: 57.5-79.9%), Odds Ratio: 1.00 (95%CI 0.47-2.15; p > 0.9). No advantage in favor of EZ arm over E arm emerged either in terms of PFS (Hazard Ratio [HR] 0.77, 95%CI 0.44-1.37; p = 0.4) or OS (HR 1.09; 95%CI 0.54-2.2; p = 0.8). A main limitation of this study was the inability of WB-DW-MRI to evaluate disease response in 17 patients.
ZA did not improve bone response rate to E plus ADT in mHSPC patients. WB-DW-MRI is a reliable technique to evaluate the response of prostate cancer bone metastases to systemic therapy.
唑来膦酸（ZA）联合雄激素剥夺疗法（ADT）在晚期前列腺癌患者中从未被证明具有额外的活性。然而，传统成像在监测转移性骨病变的疾病反应方面可靠性较差。
BonEnza是一项随机II期多中心临床试验，旨在通过全身扩散加权磁共振成像（WB-DW-MRI）比较ADT联合恩杂鲁胺（E）加/减ZA在骨反应率方面的活性。从2018年2月至2021年6月，纳入了126例骨扫描显示有转移性激素敏感性前列腺癌（mHSPC）和骨转移的患者。患者按1:1随机分组，分别接受单独口服E 160mg每日一次（E组）或联合每4周静脉注射ZA 4mg（EZ组）。该研究的主要终点是骨转移的总缓解率（ORR），次要终点是传统成像的ORR、无进展生存期（PFS）和总生存期（OS）。使用逻辑模型评估治疗组与ORR之间的关联。
中位随访31.9个月后，根据意向性分析，两组的ORR相当：69.8%（95%置信区间[CI]：57.5 - 79.9%），优势比：1.00（95%CI 0.47 - 2.15；p＞0.9）。在PFS（风险比[HR] 0.77，95%CI 0.44 - 1.37；p = 0.4）或OS（HR 1.09；95%CI 0.54 - 2.2；p = 0.8）方面，EZ组相对于E组均未显示出优势。本研究的一个主要局限性是WB-DW-MRI无法评估17例患者的疾病反应。
ZA并未提高mHSPC患者对E加ADT的骨反应率。WB-DW-MRI是评估前列腺癌骨转移对全身治疗反应的可靠技术。
