Afriansyah Andika, Hamid Agus Rizal Ah, Mochtar Chaidir A, Umbas Rainy
Department of Urology, Faculty of Medicine, Universitas Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
Acta Med Indones. 2016 Oct;48(4):335-347.
In the past 10 years, recent development of targeted therapy in metastatic renal cell carcinoma (mRCC) has provided a new hope and significantly enhanced the prognosis of the disease. Three class of targeted therapy were developed, including multi-targeted tyrosine kinase inhibitors (TKI), the mammalian target of rapamycin (mTOR) complex-1 kinase inhibitors, and the humanized antivascular endothelial growth factor (VEGF) monoclonal antibody. Hence, the objective of this article was to critically examine the current evidence of targeted therapy treatment for patients with mRCC. In the majority of trials evaluating targeted therapy, patients were stratified according to Memorial Sloan Kattering Cancer Center (MSKCC) risk model and the recommendation of targeted treatment based on risk features. In first-line setting (no previous treatment), sunitinib, pazopanib, or bevacizumab plus IFN-α were recommended as treatment options for patient with favorable- or intermediate- risk features and clear cell histology. Patients who progressed after previous cytokine therapy would have sorafenib or axitinib as treatment options. Clear-cell mRCC with favorable- or intermediate- risk features and failure with first-line TKI therapy might be treated with sorafenib, everolimus, temsirolimus or axitinib. However, the current evidence did not show the best treatment sequencing after first-line TKI failure. In patients with poor-risk clear-cell and non-clear cell mRCC, temsirolimus was the treatment option supported by phase III clinical trial. In addition, several new drugs, nowadays, are still being investigated and waiting for the result of phase II or III clinical trial, and this might change the standard therapy for mRCC in the future.
在过去10年中,转移性肾细胞癌(mRCC)靶向治疗的最新进展带来了新的希望,并显著改善了该疾病的预后。已开发出三类靶向治疗药物,包括多靶点酪氨酸激酶抑制剂(TKI)、雷帕霉素哺乳动物靶点(mTOR)复合物1激酶抑制剂以及人源化抗血管内皮生长因子(VEGF)单克隆抗体。因此,本文的目的是严格审查mRCC患者靶向治疗的现有证据。在大多数评估靶向治疗的试验中,患者根据纪念斯隆凯特琳癌症中心(MSKCC)风险模型进行分层,并根据风险特征进行靶向治疗推荐。在一线治疗(未接受过先前治疗)中,舒尼替尼、帕唑帕尼或贝伐单抗加干扰素-α被推荐作为具有良好或中等风险特征且组织学类型为透明细胞的患者的治疗选择。先前接受细胞因子治疗后病情进展的患者可选择索拉非尼或阿昔替尼。具有良好或中等风险特征且一线TKI治疗失败的透明细胞mRCC患者可能接受索拉非尼、依维莫司、替西罗莫司或阿昔替尼治疗。然而,现有证据并未显示一线TKI治疗失败后的最佳治疗顺序。对于具有高风险透明细胞和非透明细胞mRCC的患者,替西罗莫司是III期临床试验支持的治疗选择。此外,目前仍有几种新药正在研究中,等待II期或III期临床试验结果,这可能会改变未来mRCC的标准治疗方法。