Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer
Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer
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DOI：
10.1200/jco.2017.76.9901
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发表时间：
2018-03-10
影响因子：
45.3
通讯作者：
Andre, Thierry
中科院分区：
文献类型：
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作者：
Overman, Michael J.;Lonardi, Sara;Andre, Thierry
纳武单抗在既往接受过治疗的DNA错配修复缺陷（dMMR）/微卫星不稳定性高（MSI-H）转移性结直肠癌（mCRC）患者中提供临床获益（客观缓解率[ORR]，31%; 95%CI，20.8 - 42.9;疾病控制率，69%; 12个月总生存期[OS]，73%）;纳武单抗联合伊匹单抗可能改善这些结局。CheckMate-142的nivolumab加ipilimumab队列的功效和安全性结果是dMMR/MSI-H mCRC.Patients和MethodsPatients的免疫疗法组合的最大的单研究报告，每3周一次（四个剂量）接受nivolumab 3 mg/kg加ipilimumab 1 mg/kg，随后每2周一次接受nivolumab 3 mg/kg。主要终点是化疗药物评估的ORR.ResultsOf 119例患者，76%接受过两次既往全身治疗。中位随访13.4个月时，评估者评估的ORR为55%（95%CI，45.2 - 63.8），12周的疾病控制率为80%。未达到中位缓解持续时间;大多数缓解（94%）在数据截止时仍在持续。无进展生存率分别为76%（9个月）和71%（12个月）; OS率分别为87%和85%。在患者报告的结局（包括功能、症状和生活质量）中观察到统计学显著和有临床意义的改善。32%的患者发生了3 - 4级治疗相关不良事件（AE），并且是可管理的。因研究药物相关AE而中止治疗的患者（13%）的ORR（63%）与总体population.ConclusionNivolumab加ipilimumab表现出高应答率，鼓励无进展生存期和12个月OS，可控的安全性，以及关键患者报告结局的有意义改善。间接比较表明，联合治疗相对于抗程序性死亡-1单药治疗提供了改善的疗效，并且具有有利的获益-风险特征。Nivolumab联合ipilimumab为dMMR/MSI-H mCRC患者提供了一种有希望的新治疗选择。(C)2018年美国临床肿瘤学会
PurposeNivolumab provides clinical benefit (objective response rate [ORR], 31%; 95% CI, 20.8 to 42.9; disease control rate, 69%; 12-month overall survival [OS], 73%) in previously treated patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC); nivolumab plus ipilimumab may improve these outcomes. Efficacy and safety results for the nivolumab plus ipilimumab cohort of CheckMate-142, the largest single-study report of an immunotherapy combination in dMMR/MSI-H mCRC, are reported.Patients and MethodsPatients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks. Primary end point was investigator-assessed ORR.ResultsOf 119 patients, 76% had received two prior systemic therapies. At median follow-up of 13.4 months, investigator-assessed ORR was 55% (95% CI, 45.2 to 63.8), and disease control rate for 12 weeks was 80%. Median duration of response was not reached; most responses (94%) were ongoing at data cutoff. Progression-free survival rates were 76% (9 months) and 71% (12 months); respective OS rates were 87% and 85%. Statistically significant and clinically meaningful improvements were observed in patient-reported outcomes, including functioning, symptoms, and quality of life. Grade 3 to 4 treatment-related adverse events (AEs) occurred in 32% of patients and were manageable. Patients (13%) who discontinued treatment because of study drug-related AEs had an ORR (63%) consistent with that of the overall population.ConclusionNivolumab plus ipilimumab demonstrated high response rates, encouraging progression-free survival and OS at 12 months, manageable safety, and meaningful improvements in key patient-reported outcomes. Indirect comparisons suggest combination therapy provides improved efficacy relative to anti-programmed death-1 monotherapy and has a favorable benefit-risk profile. Nivolumab plus ipilimumab provides a promising new treatment option for patients with dMMR/MSI-H mCRC. (C) 2018 by American Society of Clinical Oncology