Primary anti-vascular endothelial growth factor (VEGF)-refractory metastatic renal cell carcinoma: clinical characteristics, risk factors, and subsequent therapy
Primary anti-vascular endothelial growth factor (VEGF)-refractory metastatic renal cell carcinoma: clinical characteristics, risk factors, and subsequent therapy
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DOI：
10.1093/annonc/mdr533
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发表时间：
2012-06-01
影响因子：
50.5
通讯作者：
Choueiri, T. K.
中科院分区：
文献类型：
--
作者：
Heng, D. Y.;MacKenzie, M. J.;Choueiri, T. K.
背景资料：根据RECIST标准，接受初始抗血管内皮生长因子（VEGF）治疗的一部分患者表现出疾病进展（PD）作为最佳缓解。方法：通过国际mRCC数据库联盟从12个中心收集接受抗VEGF治疗的转移性肾细胞癌（mRCC）患者的数据。结果：1000五十六例可评估患者接受了初始VEGF抑制剂治疗，其中272例（26%）患者的最佳缓解为PD。初始治疗包括舒尼替尼（n = 203）、索拉非尼（n = 51）或贝伐珠单抗（n = 18）。6%的患者处于有利风险，55%处于中等风险，39%处于不良风险。多因素分析显示，帕金森病的预测因素为Karnofsky体力状态<80%[OR = 2.3，P <0.0001]，诊断至治疗时间<1年（OR = 2.1，P <0.0001）、嗜中性粒细胞增多（OR = 1.9，P = 0.0021）、血小板增多（OR = 1.7，P = 0.0068）和贫血（OR = 1.6，P = 0.0058）。PD患者与非PD患者的中位无进展生存期（PFS）分别为2.4个月与11个月（P <0.0001），总生存期（OS）分别为6.8个月与29个月（P <0.0001）。108例（40%）VEGF难治性患者继续接受进一步的全身治疗。随后治疗的反应率，PFS和OS分别为9%，2.5个月和7.4个月，接受VEGF与哺乳动物雷帕霉素靶蛋白（mTOR）inhibitors. Conclusions：原发性抗VEGF难治性mRCC患者预后不良。二线抗mTOR和抗VEGF药物产生相似的结果。
Background: A subset of patients treated with initial anti-vascular endothelial growth factor (VEGF) therapy exhibit progressive disease (PD) as the best response per RECIST criteria.Methods: Data from patients with metastatic renal cell carcinoma (mRCC) treated with anti-VEGF therapy were collected through the International mRCC Database Consortium from 12 centers.Results: One thousand and fifty-six assessable patients received initial VEGF inhibitors and 272 (26%) of these patients had PD as best response. Initial treatment included sunitinib (n = 203), sorafenib (n = 51), or bevacizumab (n = 18). Six percent of patients were at favorable risk, 55% at intermediate risk, and 39% at poor risk. On multivariable analysis, predictors of PD were Karnofsky performance status < 80% [odds ratio (OR) = 2.3, P < 0.0001], diagnosis to treatment < 1 year (OR = 2.1, P < 0.0001), neutrophilia (OR = 1.9, P = 0.0021), thrombocytosis (OR = 1.7, P = 0.0068), and anemia (OR = 1.6, P = 0.0058). Median progression-free survival (PFS) in patients with PD versus without PD was 2.4 versus 11 months (P < 0.0001) and overall survival (OS) was 6.8 versus 29 months (P < 0.0001), respectively. One hundred and eight (40%) VEGF-refractory patients proceeded to receive further systemic therapies. Response rate, PFS, and OS for subsequent therapy were 9%, 2.5 months, and 7.4 months, respectively, with no statistical differences between patients who received VEGF versus mammalian target of rapamycin (mTOR) inhibitors.Conclusions: Primary anti-VEGF-refractory mRCC patients have a dismal prognosis. Second-line anti-mTOR and anti-VEGF agents produce similar outcomes.