《新英格兰医学杂志》2018年3月21日在线先发

晚期肾细胞癌中纳武单抗+Ipilimumab与舒尼替尼的疗效对比

背景

在一项初步研究中，纳武单抗+Ipilimumab使晚期肾细胞癌患者产生了客观缓解。这项3期临床试验针对初治的晚期肾透明细胞癌，比较了纳武单抗+Ipilimumab与舒尼替尼的疗效。

方法

我们按1：1比例，将成年患者随机分组，一组接受纳武单抗(3mg/kg体重)+ipilimumab（1mg/kg），1次/3周，静脉注射，共4次剂量，序贯纳武单抗(3mg/kg)，1次/2周；另一组口服舒尼替尼50mg，1次/天，用4个星期(6个星期为一疗程)。主要终点为有中高危预后风险的患者的总生存(α水平，0.04)、客观缓解率(α水平，0.001)和无进展生存(α水平，0.009)。

结果

共计对1096名患者分组接受治疗，纳武单抗+ipilimumab组550名，舒尼替尼组546名，分别有425名、422名患者为中高危。中高危患者中位随访25.2个月，纳武单抗+ipilimumab组18个月时总生存率为75%（95%置信区间[CI]，70-78），舒尼替尼组60%（95%CI,55-65）；纳武单抗+ipilimumab组中位总生存期未到，舒尼替尼组为26.0个月(死亡风险比为0.63，P<0.001)；客观缓解率为42%对27%（P<0.001），完全缓解率为9%对比1%；中位无进展生存期分别为11.6个月和8.4个月(疾病进展或死亡的风险比，0.82；P=0.03，按照预先确定的0.009阈值，无显著差异）。纳武单抗+ipilimumab组547名患者中有509名（93%）出现了治疗相关性不良反应，而舒尼替尼组535名患者中有521名(97%)；分别有250名(46%)和335名(63%)患者出现了≥3级的不良反应，导致停药的治疗相关不良反应发生率分别为22%和12%。

结论

在初治的中高危晚期肾细胞癌患者中，与舒尼替尼相比，纳武单抗+ipilimumab的总生存率和客观缓解率均明显提高。(百时美施贵宝和小野药业资助，ClinicalTrials.gov网站注册号NCT02231749）。

《壹篇》白红松

Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma

Background

Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma.

Methods

We randomly assigned adults in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The coprimary end points were overall survival (alpha level,0.04), objective response rate (alpha level,0.001), and progression-free survival (alpha level,0.009) among patients with intermediate or poor prognostic risk.

Results

A total of 1096 patients were assigned to receive nivolumab plus ipilimumab (550 patients) or sunitinib (546 patients); 425 and 422, respectively, had intermediate or poor risk. At a median follow-up of 25.2 months in intermediate- and poor-risk patients, the 18-month overall survival rate was 75% (95% confidence interval [CI], 70 to 78) with nivolumab plus ipilimumab and 60% (95% CI, 55 to 65) with sunitinib; the median overall survival was not reached with nivolumab plus ipilimumab versus 26.0 months with sunitinib (hazard ratio for death, 0.63; P<0.001). The objective response rate was 42% versus 27% (P<0.001), and the complete response rate was 9% versus 1%. The median progression-free survival was 11.6 months and 8.4 months, respectively (hazard ratio for disease progression or death, 0.82; P=0.03, not significant per the prespecified 0.009 threshold). Treatment-related adverse events occurred in 509 of 547 patients (93%) in the nivolumab-plus-ipilimumab group and 521 of 535 patients (97%) in the sunitinib group; grade 3 or 4 events occurred in 250 patients (46%) and 335 patients (63%), respectively. Treatment-related adverse events leading to discontinuation occurred in 22% and 12% of the patients in the respective groups.

Conclusions

Overall survival and objective response rates were significantly higher with nivolumab plus ipilimumab than with sunitinib among intermediate- and poor-risk patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 214 ClinicalTrials.gov number, NCT02231749.)

《壹篇》（与微信公众号“桓兴医讯”同步）系主要面向医务人员的公益性头条号，不以营利为目的，不进行任何有偿和无偿咨询服务，不出售任何产品，与ASCO、CSCO等所有专业学会和机构没有任何关系和联系，也不代表任何官方学会发声。欢迎转载，以让更多的专业人员了解医学前沿进展。

文章图片均来自网络，不做商业用途，若有版权争议请与《壹篇》联系。

坚持点赞、赞赏和转发是一种态度和支持。