骨靶向治疗对转移性肾细胞癌患者有益吗？
Does Bone-targeted Therapy Benefit Patients with Metastatic Renal Cell Carcinoma?
作者信息
Wong Emily C L, Kapoor Anil
机构信息
Department of Surgery, Division of Urology, McMaster University, Hamilton, Ontario, Canada.
Department of Surgery, Division of Urology, McMaster University, Hamilton, Ontario, Canada.
出版信息
Transl Oncol. 2020 Feb;13(2):241-244. doi: 10.1016/j.tranon.2019.10.009. Epub 2019 Dec 21.
INTRODUCTION
In metastatic renal cell carcinoma (mRCC), the bone is the second most common site of metastasis and is associated with increased morbidity and poorer quality of life. Bone-targeted therapies (BTTs) such as denosumab and zoledronic acid may prevent skeletal-related events (SREs). However, the benefit of BTTs in combination with tyrosine kinase inhibitors (TKIs) remains unclear.
METHODS
We performed a retrospective chart review at the Urologic Cancer Centre for Research and Innovation. Patients with mRCC were included if they had bone metastases treated with TKIs between 2010 and 2017. Our primary outcome was overall survival (OS), defined as the time elapsed from clinical diagnosis of mRCC to death, and modelled using the Kaplan-Meier method. Secondary outcomes included the median time to SRE and the analysis of prognostic factors of OS using Cox proportional hazards regression.
RESULTS
In total, 230 patients with mRCC were identified; of which, 46 had bone metastases treated with TKIs and were included in the study (TKI-only, n = 37; TKI + BTT, n = 9). In the TKI + BTT cohort, patients received either denosumab (n = 5) or zoledronic acid (n = 4). At the time of analysis, 63% of patients were deceased. We observed an OS trend favouring the TKI + BTT cohort (13.8 months [95% confidence interval {CI}: 12.3-15.2] vs. 29.6 months [95% CI: 7.2-51.9], hazard ratio [HR]: 1.66 (95% CI: 0.62-4.45), P = 0.31). When patients in the TKI + BTT cohort were stratified by type of therapy (denosumab or zoledronic acid), the median time to SRE was similar between the groups (4.2 months [95% CI: 2.28-6.14] vs. 2.2 months [95% CI: not available], P = 0.71]. On univariate or multivariate analysis, it was found that age, gender, comorbidities, International metastatic RCC database consortium (IMDC) prognostic group and pathologic tumour grade were not significant predictors of worse OS. Pathologic stage 3 or 4 was an independent predictor of worse OS (HR: 5.8, 95% CI: 1.41-24.03, P = 0.015).
CONCLUSION
BTTs may have a continued role in the era of targeted therapy and immunotherapy. Further prospective data are required to validate our findings.
引言
在转移性肾细胞癌（mRCC）中，骨骼是第二常见的转移部位，与发病率增加和生活质量下降相关。地诺单抗和唑来膦酸等骨靶向治疗（BTTs）可能预防骨相关事件（SREs）。然而，BTTs与酪氨酸激酶抑制剂（TKIs）联合使用的益处仍不明确。
方法
我们在泌尿外科癌症研究与创新中心进行了一项回顾性病历审查。纳入2010年至2017年间接受TKIs治疗骨转移的mRCC患者。我们的主要结局是总生存期（OS），定义为从mRCC临床诊断到死亡的时间，并使用Kaplan-Meier方法进行建模。次要结局包括至SRE的中位时间以及使用Cox比例风险回归分析OS的预后因素。
结果
共确定230例mRCC患者；其中，46例接受TKIs治疗骨转移的患者被纳入研究（仅TKIs组，n = 37；TKIs + BTT组，n = 9）。在TKIs + BTT队列中，患者接受地诺单抗（n = 5）或唑来膦酸（n = 4）治疗。在分析时，63%的患者已死亡。我们观察到OS有倾向于TKIs + BTT队列的趋势（13.8个月[95%置信区间{CI}：12.3 - 15.2] vs. 29.6个月[95% CI：7.2 - 51.9]，风险比[HR]：1.66（95% CI：0.62 - 4.45），P = 0.31）。当根据治疗类型（地诺单抗或唑来膦酸）对TKIs + BTT队列中的患者进行分层时，两组至SRE的中位时间相似（4.2个月[95% CI：2.28 - 6.14] vs. 2.2个月[95% CI：不可用]，P = 0.71）。在单因素或多因素分析中，发现年龄、性别、合并症、国际转移性RCC数据库联盟（IMDC）预后组和病理肿瘤分级不是OS较差的显著预测因素。病理分期3或4是OS较差的独立预测因素（HR：5.8，95% CI：1.41 - 24.03，P = 0.015）。
结论
BTTs在靶向治疗和免疫治疗时代可能继续发挥作用。需要进一步的前瞻性数据来验证我们的发现。
Zotero 插件