Broom Reuben J, Hinder Victoria, Sharples Katrina, Proctor Janie, Duffey Steven, Pollard Stephanie, Fong Peter C C, Forgeson Garry, Harris Dean L, Jameson Michael B, O'Donnell Anne, North Richard T, Deva Sanjeev, Hanning Fritha J, Grey Andrew, Findlay Michael P N
Regional Cancer and Blood Centre, Auckland City Hospital, Auckland, New Zealand.
Cancer Trials New Zealand, Discipline of Oncology, University of Auckland, New Zealand.
Clin Genitourin Cancer. 2015 Feb;13(1):50-8. doi: 10.1016/j.clgc.2014.07.002. Epub 2014 Jul 15.
Bone metastases from renal cell carcinoma (RCC) are a major cause of morbidity. Post hoc analysis has suggested that bone turnover markers can identify patients at risk of skeletal-related events (SREs) among those receiving zoledronic acid. This study sought to evaluate the effect on bone metastases of everolimus alone compared with everolimus plus zoledronic acid.
Thirty treatment-naive patients with RCC and ≥ 1 bone metastases were randomized 1:1 to everolimus (10 mg daily) versus everolimus plus zoledronic acid (4 mg intravenously 4-weekly). Bone-specific assessments were performed at baseline and at weeks 1, 4, 8, and 12. Treatment was continued on allocated arm until progression per RECIST 1.1 (Response Evaluation Criteria in Solid Tumors, version 1.1). The primary outcome measure was urine N-telopeptide (uNTX) level, with secondary measures of plasma C-telopeptide (CTX), quality of life (Functional Assessment of Cancer Therapy-Bone Pain [FACT-BP], Brief Pain Inventory [BPI]), progression-free survival (PFS), SREs, and safety.
After 12 weeks, reduction in mean uNTX and CTX on everolimus plus zoledronic acid relative to everolimus was 68.4% (95% CI, 60.1%-74.9%; P < .0001) and 76.2% (95% CI, 67.3%-82.7%; P < .0001), respectively. There was no evidence of a difference for FACT-BP (P = .5), but evidence was favorable for BPI Severity (P = .05) and BPI Interference (P = .06). Median PFS was 7.5 months (95% CI, 3.4-11.2) on everolimus plus zoledronic acid and 5.4 months (95% CI, 3.2-6.3) on everolimus (P = .009). Median time to first SRE was 9.6 months (95% CI, 4.3-15.5) on everolimus plus zoledronic acid and 5.2 months (95% CI, 1.6-8.2) on everolimus (P = .03).
In this RCC population, the addition of zoledronic acid to everolimus significantly reduced bone resorption markers and may prolong tumor control.
肾细胞癌（RCC）骨转移是发病的主要原因。事后分析表明，骨转换标志物可在接受唑来膦酸治疗的患者中识别出有发生骨相关事件（SREs）风险的患者。本研究旨在评估依维莫司单药与依维莫司联合唑来膦酸对骨转移的影响。
30例初治的RCC且有≥1处骨转移的患者按1:1随机分为依维莫司组（每日10 mg）和依维莫司联合唑来膦酸组（每4周静脉注射4 mg）。在基线以及第1、4、8和12周进行骨特异性评估。根据实体瘤疗效评价标准1.1版（RECIST 1.1），在分配的治疗组中持续治疗直至疾病进展。主要结局指标为尿N-端肽（uNTX）水平，次要指标包括血浆C-端肽（CTX）、生活质量（癌症治疗功能评估-骨痛量表 [FACT-BP]、简明疼痛问卷 [BPI]）、无进展生存期（PFS）、SREs以及安全性。
12周后，依维莫司联合唑来膦酸组相对于依维莫司组，平均uNTX和CTX的降低幅度分别为68.4%（95% CI，60.1%-74.9%；P <.0001）和76.2%（95% CI，67.3%-82.7%；P <.0001）。FACT-BP无差异证据（P =.5），但BPI严重程度（P =.05）和BPI干扰方面有有利证据（P =.06）。依维莫司联合唑来膦酸组的中位PFS为7.5个月（95% CI，3.4-11.2），依维莫司组为5.4个月（95% CI，3.2-6.3）（P =.009）。依维莫司联合唑来膦酸组首次发生SRE的中位时间为9.6个月（95% CI，4.3-15.5），依维莫司组为5.2个月（95% CI，1.6-8.2）（P =.03）。
在该RCC人群中，依维莫司联合唑来膦酸可显著降低骨吸收标志物水平，并可能延长肿瘤控制时间。
