Optimized Management of Nivolumab and Ipilimumab in Advanced Renal Cell Carcinoma: A Response-Based Phase II Study (OMNIVORE)
Optimized Management of Nivolumab and Ipilimumab in Advanced Renal Cell Carcinoma: A Response-Based Phase II Study (OMNIVORE)
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晚期肾细胞癌中 Nivolumab 和 Ipilimumab 的优化治疗：基于反应的 II 期研究 (OMNIVORE)
DOI：
10.1200/jco.20.02295
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发表时间：
2020-12-20
影响因子：
45.3
通讯作者：
Choueiri, Toni K.
中科院分区：
文献类型：
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作者：
McKay, Rana R.;McGregor, Bradley A.;Choueiri, Toni K.
在这个II期反应适应性试验中，我们研究了免疫检查点阻断在肾细胞癌（RCC; ClinicalTrials.gov标识符：NCT 03203473）中的合理应用。所有患者均单独接受纳武单抗治疗，随后根据缓解情况进行分组。在6个月内确认部分反应（PR）或完全反应（CR）的患者停用纳武单抗并进行观察（A组）。在纳武单抗治疗不超过6个月后疾病稳定或疾病进展（PD）的患者接受两剂伊匹单抗（组B）。主要终点是在nivolumab停药后1年时具有PR/CR的患者比例（A组）和在ipilimumab后转化为PR/CR的nivolumab无应答者比例（B组）。总体而言，83名患者开始治疗，其中96%具有透明细胞组织学，51%为未经治疗，67%具有中等/低风险疾病。中位随访时间为19.5个月。在6个月内，诱导nivolumab导致12%的患者（n = 10）确认PR。14例患者未分配至研究组（7例因毒性，7例因PD）。12名患者（14%）被分配到A组并停用nivolumab，其中5名（42%; 90% CI，18%至68%）在>= 1年时仍停用nivolumab。在分配至B组的57名患者中（69%），2名患者转化为确认的PR（4%; 90%CI，1%至11%），并且未观察到CRs. CONCLUSION在本研究中，nivolumab随后两次剂量的ipilimumab导致无CR和低PR/CR转化。评估nivolumab停药的患者数量太少，无法评估这种方法的价值。目前，我们的数据不支持在晚期RCC中用于检查点阻断的响应自适应策略。
PURPOSEIn this phase II response-adaptive trial, we investigated the rational application of immune checkpoint blockade in renal cell carcinoma (RCC; ClinicalTrials.gov identifier: NCT03203473).METHODSWe enrolled patients with metastatic RCC with no prior checkpoint inhibitor exposure. All patients received nivolumab alone with subsequent arm allocation based on response. Patients with a confirmed partial response (PR) or complete response (CR) within 6 months discontinued nivolumab and were observed (arm A). Patients with stable disease or progressive disease (PD) after no more than 6 months of nivolumab received two doses of ipilimumab (arm B). The primary endpoints were the proportion of patients with PR/CR at 1 year after nivolumab discontinuation (arm A) and proportion of nivolumab nonresponders who converted to PR/CR after ipilimumab (arm B).RESULTSOverall, 83 patients initiated treatment, of whom 96% had clear-cell histology, 51% were treatment naive, and 67% had intermediate/poor-risk disease. Median follow-up was 19.5 months. Within 6 months, induction nivolumab resulted in a confirmed PR in 12% of patients (n = 10). Fourteen patients were not allocated to a study arm (seven because of toxicity, seven because of PD). Twelve patients (14%) were allocated to arm A and discontinued nivolumab, of whom five (42%; 90% CI, 18% to 68%) remained off nivolumab at >= 1 year. Of 57 patients (69%) allocated to arm B, two patients converted to a confirmed PR (4%; 90% CI, 1% to 11%), and no CRs were observed.CONCLUSIONIn this study, nivolumab followed by two doses of ipilimumab resulted in no CRs and a low PR/CR conversion. The number of patients evaluated for nivolumab discontinuation was too small to assess the value of this approach. Currently, our data do not support a response-adaptive strategy for checkpoint blockade in advanced RCC.