索拉非尼和舒尼替尼一线治疗转移性肾癌的疗效比较及预后分析

Comparison of efficacy between sorafenib and sunitinib as first-line therapy for metastatic renal cell carcinoma and analyze prognostic factors for survival

目的评价索拉非尼和舒尼替尼作为一线酪氨酸激酶抑制剂（TKI）治疗转移性肾癌的疗效和安全性，并探讨患者预后的影响因素。方法回顾性分析271例临床病理资料完整的转移性肾癌患者的资料，其中索拉非尼组174例，舒尼替尼组97例，评价索拉非尼组和舒尼替尼组的疗效和不良反应。采单因素和多因素Cox比例风险模型分析预后影响因素。结果索拉非尼组和舒尼替尼组的客观反应率分别为14.9%和19.6 %，疾病控制率分别为85.1%和88.6%，两组差异均无统计学意义（P值分别为0.325和0.408）。索拉非尼组最常见的3～4级不良反应为手足综合征（6.7%）、腹泻（2.3%）和皮疹（2.3%）。舒尼替尼组最常见的3～4级不良反应为中性粒细胞下降（6.2%）、手足综合征（6.2%）和血小板下降（4.6%）。随访期间，索拉非尼组死亡97例，疾病进展81例。中位无进展生存时间（PFS）为12个月（95%CI：9～15个月），中位总生存时间（OS）为25个月（95%CI：21～29个月）。舒尼替尼组死亡74例，疾病进展40例。中位PFS为12个月（95%CI：10～12个月），中位OS为23个月（95%CI：20～32个月）。两组PFS和OS差异均无统计学意义（P值分别为0.771和0.548）。多因素分析显示，Fuhrman分级（HR=1.358，95%CI：1.004～1.835）、转移器官数（HR=1.550，95%CI：1.143～2.101）及（纪念斯隆-凯特林癌症中心MSKCC）危险分级（中危组：HR =1.621，95%CI：1.117～2.232；高危组：HR=2.890，95%CI：1.942～4.298）是转移性肾癌患者PFS的独立影响因素。Fuhrman分级（HR=2.135，95%CI：1.533～2.974）、转移器官数（HR=1.774，95%CI：1.279～2.461）及MSKCC危险分级（中危组：HR=1.415，95%CI：1.002～1.998；高危组：HR=3.161，95%CI：2.065～4.838）是转移性肾癌患者OS的独立影响因素。结论 索拉非尼与舒尼替尼作为一线TKI药物治疗转移性肾癌疗效显著，两者疗效无明显差异，药物相关不反应分布有所不同。Fuhrman分级、转移器官数和MSKCC评分是转移性肾癌患者预后的独立影响因素。

Objective To investigate the efficacy and drug related adverse reactions of sorafenib and sunitinib as first-line tyrosine-kinase inhibitors （TKIs） for patients with metastatic renal cell carcinoma （mRCC） and analyze the clinical prognostic factor for survival.Methods The data of 271 patients with metastatic renal cell carcinoma who had complete clinicopathological data were retrospectively analyzed, including 174 cases in sorafenib group and 97 cases in sunitinib group, to access patients′ overall survival （OS） and progression-free survival （PFS）. Prognostic values of all characteristics were determined by using univariate and multivariate Cox regression models. Results The objective response rates （ORR） of the sorafenib and sunitinib groups were 14.9% and 19.6%, respectively, and the disease control rates （DCR） were 85.1% and 88.6%, respectively. No significant difference was found between the sorafenib and sunitinib group in ORR （P=0.325） or DCR （P=0.408）. The most common grade 3 to 4 adverse events in the sorafenib group were hand-foot syndrome （6.7%）, diarrhea （2.3%）, and rash （2.3%）. The most common grade 3 to 4 adverse events in the sunitinib group were neutropenia （6.2%）, hand-foot syndrome （6.2%）, and thrombocytopenia （4.6%）. During the follow-up, 97 cases death occurred and 81 cases disease progression occurred in sorafenib group. The median PFS was 12 months （95% CI： 9-15 months）, and the median OS was 25 months （95% CI： 21-29 months） in sorafenib group. While 74 cases death occurred and 40 cases disease progression occurred in sunitinib group, the median PFS was 12 months （95% CI： 10-12 months） and the median OS was 23 months （95% CI： 20-32 months） in sunitinib group. No significant difference was found between the sorafenib and the sunitinib group in PFS （P=0.771） or OS （P=0.548）. Multivariate analysis showed Fuhrman grades （HR=1.358, 95%CI： 1.004-1.835）, number of metastatic sites （HR=1.550, 95%CI： 1.143-2.101） and MSKCC risk grade （Intermediate risk group： HR=1.621, 95%CI： 1.117-2.232; Poor risk group： HR=2.890, 95%CI： 1.942-4.298） were independent prognostic factors for PFS. Fuhrman grades （HR=2.135, 95%CI： 1.533-2.974）, number of metastatic sites （HR=1.774, 95%CI： 1.279-2.461） and MSKCC risk grade （Intermediate risk group： HR=1.415, 95%CI： 1.002-1.998; Poor risk group： HR=3.161, 95%CI： 2.065-4.838） were independent prognostic factors for OS.Conclusions The results of this study indicate that sorafenib and sunitinib are both effective as the first-line TKIs for mRCC patients and sorafenib has comparable efficacy to sunitinib. But they have differences in the incidence of adverse effects. Fuhrman grades, number of metastatic sites and MSKCC risk grade are independent prognostic factors for mRCC patients.