Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057)
Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057)
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DOI：
10.1200/jco.2017.74.3062
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发表时间：
2017-12-10
影响因子：
45.3
通讯作者：
Eberhardt, Wilfried E. E.
中科院分区：
文献类型：
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作者：
Horn, Leora;Spigel, David R.;Eberhardt, Wilfried E. E.
在两项独立的III期研究中，与多西他赛相比，Nivolumab（程序性死亡-1抑制剂）延长了既往接受过治疗的晚期鳞状（CheckMate 017; ClinicalTrials.gov标识符：NCT 01642004）或非鳞状（CheckMate 057; ClinicalTrials.gov标识符：NCT 01673867）非小细胞肺癌（NSCLC）患者的总生存期。我们报告最新的结果，包括汇总分析的两个study.MethodsPatients IIIB/IV鳞状（N = 272）或非鳞状（N = 582）NSCLC和疾病进展期间或之后，以前铂为基础的化疗随机分配1：1 nivolumab（3 mg/kg每2周）或多西他赛（75 mg/m2每3周）。最低随访生存期为24.2个月。结果纳武利尤单抗组与多西他赛组的2年总生存率为23%（95% CI，16%-30%）vs 8%（95% CI，4%-13%），鳞状NSCLC和29%（95%CI，24%至34%）vs 16%（95% CI，12%-20%）;与多西他赛相比，纳武利尤单抗的死亡风险相对降低与主要分析中报告的结果相似。纳武利尤单抗观察到持久的缓解; 27例确诊的鳞状NSCLC缓解者中有10例（37%），56例非鳞状NSCLC缓解者中有19例（34%）在至少2年随访后持续缓解。两个多西他赛组均无患者持续缓解。在汇总分析中，与多西他赛相比，纳武利尤单抗的死亡风险相对降低28%（风险比，0.72; 95%CI，0.62至0.84），纳武利尤单抗治疗相关不良事件的发生率低于多西他赛结论与多西他赛相比，纳武利尤单抗在既往接受过治疗的晚期NSCLC患者中提供了长期的临床获益和良好的耐受性。
PurposeNivolumab, a programmed death-1 inhibitor, prolonged overall survival compared with docetaxel in two independent phase III studies in previously treated patients with advanced squamous (CheckMate 017; ClinicalTrials.gov identifier: NCT01642004) or nonsquamous (CheckMate 057; ClinicalTrials.gov identifier: NCT01673867) non-small-cell lung cancer (NSCLC). We report updated results, including a pooled analysis of the two studies.MethodsPatients with stage IIIB/IV squamous (N = 272) or nonsquamous (N = 582) NSCLC and disease progression during or after prior platinum-based chemotherapy were randomly assigned 1:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m(2) every 3 weeks). Minimum follow-up for survival was 24.2 months.ResultsTwo-year overall survival rates with nivolumab versus docetaxel were 23% (95% CI, 16% to 30%) versus 8% (95% CI, 4% to 13%) in squamous NSCLC and 29% (95% CI, 24% to 34%) versus 16% (95% CI, 12% to 20%) in nonsquamous NSCLC; relative reductions in the risk of death with nivolumab versus docetaxel remained similar to those reported in the primary analyses. Durable responses were observed with nivolumab; 10 (37%) of 27 confirmed responders with squamous NSCLC and 19 (34%) of 56 with nonsquamous NSCLC had ongoing responses after 2 years' minimum follow-up. No patient in either docetaxel group had an ongoing response. In the pooled analysis, the relative reduction in the risk of death with nivolumab versus docetaxel was 28% (hazard ratio, 0.72; 95% CI, 0.62 to 0.84), and rates of treatment-related adverse events were lower with nivolumab than with docetaxel (any grade, 68% v 88%; grade 3 to 4, 10% v 55%).ConclusionNivolumab provides long-term clinical benefit and a favorable tolerability profile compared with docetaxel in previously treated patients with advanced NSCLC.