European Medicines Agency, Amsterdam, Netherlands.
Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain.
ESMO Open. 2020 Nov;5(6):e000798. doi: 10.1136/esmoopen-2020-000798.
On the 15 November 2018, the Committee for Medicinal Products for Human Use adopted an extension to an existing indication for the use of nivolumab (Opdivo) in combination with ipilimumab (Yervoy) for the first-line treatment of adult patients with intermediate/poor-risk advanced renal cell carcinoma (RCC). The approval was based on results from the Pivotal CA209214 study, a randomised, open-label, phase III study, comparing nivolumab +ipilimumab with sunitinib in subjects≥18 years of age with previously untreated advanced RCC (not amenable for surgery or radiotherapy) or metastatic RCC, with a clear-cell component. A total of 1096 patients were randomised in the trial, of which 847 patients had intermediate/poor-risk RCC and received either nivolumab (n=425) in combination with ipilimumab administered every 3 weeks for 4 doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks or sunitinib (n=422) administered orally for 4 weeks followed by 2 weeks off, every cycle. A statistically significant difference in overall survival (OS) was observed in the nivolumab + ipilimumab group compared with the sunitinib group in intermediate/poor-risk subjects (HR 0.63 (99.8% CI 0.44 to 0.89); stratified log-rank 2-sided p-value<0.0001). The median OS was not reached for the nivolumab + ipilimumab group and was 25.95 months for the sunitinib group. The OS rates were 89.5% and 86.2% at 6 months, and 80.1% and 72.1% at 12 months in the nivolumab +ipilimumab and the sunitinib groups, respectively. K-M curves separated after approximately 3 months, favouring nivolumab + ipilimumab. This was not mirrored in the favourable-risk patients where no statistically significant difference was observed between nivolumab + ipilimumab and sunitinib in favourable-risk patients (HR 1.45 (descriptive 99.8% CI 0.51 to 4.12), p =0.2715).
2018 年 11 月 15 日，人用药品委员会通过了对 nivolumab（Opdivo）联合 ipilimumab（Yervoy）用于治疗成人中/高危晚期肾细胞癌（RCC）一线治疗的现有适应证的扩展。该批准基于 Pivotal CA209214 研究的结果，这是一项随机、开放标签、III 期研究，比较了 nivolumab + ipilimumab 与舒尼替尼在未经治疗的晚期 RCC（不适合手术或放疗）或转移性 RCC 患者中的疗效，这些患者具有明确的细胞成分。共有 1096 名患者参与了该试验，其中 847 名患者患有中/高危 RCC，他们随机接受 nivolumab（n=425）联合每 3 周给予 4 剂 ipilimumab，然后每 2 周给予 nivolumab 单药 3mg/kg，或舒尼替尼（n=422）口服，每 4 周给药 1 周，停药 2 周，每周期给药。在中/高危患者中，与舒尼替尼组相比，nivolumab + ipilimumab 组的总生存期（OS）有统计学显著差异（HR 0.63（99.8%CI 0.44 至 0.89）；分层对数秩双侧检验 p 值<0.0001）。nivolumab + ipilimumab 组的中位 OS 未达到，而舒尼替尼组为 25.95 个月。nivolumab + ipilimumab 组的 6 个月 OS 率为 89.5%，12 个月 OS 率为 80.1%；而舒尼替尼组的 6 个月 OS 率为 86.2%，12 个月 OS 率为 72.1%。K-M 曲线在大约 3 个月后分开，有利于 nivolumab + ipilimumab。在低危患者中则没有观察到 nivolumab + ipilimumab 和舒尼替尼之间的统计学差异，这与之前的结果并不相符（HR 1.45（描述性 99.8%CI 0.51 至 4.12），p=0.2715）。
