[ASCO2016]聚焦中国：Anlotinib治疗转移性肾细胞癌的疗效

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2016年美国临床肿瘤学会（ASCO）年会将于6月3日至7日在美国芝加哥举行。ASCO大会摘要发布了一项由我国中国医学科学院肿瘤医院周爱平教授团队进行的Anlotinib对既往接受Anti-VEGFR酪氨酸激酶抑制剂（TKI）治疗的转移性肾细胞癌(mRCC)的疗效性研究（摘要号e16082）。研究详情如下：

成纤维细胞生长因子（FGF）信号分子可调节肿瘤生长，促进血管形成，介导部分VEGFR抑制剂抗血管生成作用。研究证明，序贯TKI治疗可有效治疗某些既往接受TKI治疗无效的mRCC患者。Anlotinib是一种强效小分子TKI口服药，靶向作用于VEGFR1/2/3，FGFR2，I期临床试验表明该药安全性较好。该多中心II期临床试验（NCT02072044）评估了Anlotinib治疗既往接受Anti-VEGFR TKI无效的mRCC（透明细胞为主）患者的有效性。

研究共纳入43例既往接受索拉非尼或舒尼替尼治疗病情进展或不能耐受的患者（1例患者在开始治疗前退出研究）。给予Anlotinib 12 mg/天，口服，治疗2周，间歇1周。主要终点为无进展生存期（PFS）。次要终点包括：总生存期（OS），总缓解率（ORR）和安全性。

研究结果

接受Anlotinib治疗的42例患者中，既往接受索拉非尼或舒尼替尼治疗后病情进展者30例，不能耐受者10例。研究数据截止至2015年5月15日。整组患者的中位PFS为11.8个月（95%CI 8.5-），既往接受TKI治疗病情进展者中位PFS为8.5个月（95%CI 4.4-），既往接受TKI治疗不能耐受者中位PFS未达到。意向性治疗（ITT）患者ORR为19.1%（95%CI 8.60-34.12）。 6周疾病控制率为90.5%（95%CI 77.4%-97.3%）。最常见的不良事件（包括所有等级）有：高血压45.2%，手足皮肤反应42.9%，乏力35.7%，蛋白尿35.7%，厌食33.3%，甲状腺功能减退28.6%，声音嘶哑23.8%，高甘油三酯血症21.3%，高胆固醇血症21.4%，口腔粘膜炎21.4%，皮疹21.4%，血小板减少14.3%。最常见的3或4级不良事件包括：淋巴细胞减少症7.1%，高血压4.8%，甲减4.8%。

研究结论

初步研究结果表明，Anlotinib对既往接受索拉非尼或舒尼替尼无效的转移性RCC患者具有有效性，且药毒性小。临床试验信息：NCT02072044。 

会议专题》》》2016年ASCO年会专题报道

摘要原文

Abstract No:e16082

Anlotinib in metastatic renal cell carcinoma (mRCC) with a previous anti-VEGFR TKI: Preliminary results from a multicenter, phase II trial

Author(s): Ai-Ping Zhou, Yuxian Bai, Yan Song, et al.

Background: Fibroblast growth factor (FGF) signaling regulates tumor growth and vascularization and partly mediates antiangiogenic escape from VEGFR inhibitors. Sequential TKI treatment has been proved to be effective in some patients with mRCC failed with a previous TKI. Anlotinib is a potent oral, small molecular TKI with a favorable safety profile in phase I trial which mainly targets VEGFR1/2/3, FGFR2. This multicenter phase II trial (NCT02072044) evaluated the efficacy of anlotinib in mRCC patients with clear cell being the predominant component who failed with a previous anti-VEGFR TKI. 

Methods: Patients who progressed on or were intolerant to sorafenib or sunitinib were enrolled. Anlotinib was administered orally at dose of 12 mg daily for 2 weeks followed by 1 week rest. The primary endpoint was PFS. Secondary end points included OS, ORR, safety. 

Results: Of 43 patients enrolled, 1 patient withdrawn his informed consent before treatment started. Of 42 patients received anlotinib, 30 patients had disease progression on and 10 were intolerant to previous sofafenib or sunitinib treatment. Data cutoff was May 15, 2015. Median PFS was 11.8 (95% CI, 8.5- ) months for the whole group, while 8.5 (95% CI, 4.4- ) months for those progressed on previous TKI treatment, not reached for those intolerant to previous TKI treatment. Overall response rate (ORR) for intent-to-treatment patients (ITT) was 19.1% (95%CI, 8.60-34.12). 6-week disease control rate was 90.5% (95%CI, 77.4%-97.3%). The most frequently reported treatment-related adverse events of all grades included hypertension 45.2%, hand-foot skin reaction 42.9%, fatigue 35.7%, proteinuria 35.7%, anorexia 33.3%, hypothyroidism 28.6%, hoarseness 23.8%, hypertriglyceridemia 21.3%, hypercholesterolemia 21.4%, oral mucositis 21.4%, skin rash 21.4%, thrombocytopenia 14.3%. The most common grade 3 or 4 side effects included lymphopenia 7.1%, hypertension 4.8% and hypothyroidism 4.8%. 

Conclusions: Anlotinib was preliminary shown to have promising efficacy with a favourable toxicity profile for patients with metastatic RCC who failed with previous sorafenib or sunitinib. Clinical trial information: NCT02072044