Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma
Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma
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DOI：
10.1056/nejmoa1802357
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发表时间：
2018-05-10
影响因子：
158.5
通讯作者：
Robert, Caroline
中科院分区：
文献类型：
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作者：
Eggermont, Alexander M. M.;Blank, Christian U.;Robert, Caroline
研究人员发现，程序性死亡1（PD-1）抑制剂pembrolizumab可延长晚期黑色素瘤患者的无进展生存期和总生存期。我们进行了一项3期双盲试验，以评估帕博利珠单抗作为切除患者的辅助治疗，高危III期黑色素瘤。方法将3例III期黑色素瘤完全切除的患者随机分组，（根据癌症分期和地理区域分层）接受200 mg派姆单抗每3周一次静脉内注射安慰剂（514名患者）或安慰剂（505名患者），共18剂（约1年）或直至疾病复发或发生不可接受的毒性作用。总体意向治疗人群和PD-1配体（PD-L1）阳性癌症患者亚组的无复发生存期是主要终点。安全性也进行了评估。在15个月的中位随访中，在总体意向治疗人群中，帕博利珠单抗与安慰剂相比，无复发生存期显著延长（1年无复发生存率，75.4% [95%置信区间{CI}，71.3至78.9] vs. 61.0% [95% CI，56.5至65.1];复发或死亡的风险比为0.57，98.4% CI为0.43 ~ 0.74; P < 0.001）和853例PD-L1阳性肿瘤患者亚组中（1年无复发生存率，帕博利珠单抗组为77.1% [95% CI，72.7至80.9]，安慰剂组为62.6% [95% CI，57.7至67.0];风险比为0.54; 95%CI，0.42至0.69; P < 0.001）。帕博利珠单抗组14.7%的患者和安慰剂组3.4%的患者报告了与试验方案相关的3至5级不良事件。有一个治疗相关的死亡，由于肌炎在pembrolizumab group. CONCLUSIONSAAs辅助治疗高危III期黑色素瘤，200毫克的pembrolizumab给药，每3周长达1年，导致显着更长的无复发生存期比安慰剂，没有新的毒性作用。
BACKGROUNDThe programmed death 1 (PD-1) inhibitor pembrolizumab has been found to prolong progression-free and overall survival among patients with advanced melanoma. We conducted a phase 3 double-blind trial to evaluate pembrolizumab as adjuvant therapy in patients with resected, high-risk stage III melanoma.METHODSPatients with completely resected stage III melanoma were randomly assigned (with stratification according to cancer stage and geographic region) to receive 200 mg of pembrolizumab (514 patients) or placebo (505 patients) intravenously every 3 weeks for a total of 18 doses (approximately 1 year) or until disease recurrence or unacceptable toxic effects occurred. Recurrence-free survival in the overall intention-to-treat population and in the subgroup of patients with cancer that was positive for the PD-1 ligand (PD-L1) were the primary end points. Safety was also evaluated.RESULTSAt a median follow-up of 15 months, pembrolizumab was associated with significantly longer recurrence-free survival than placebo in the overall intention-to-treat population (1-year rate of recurrence-free survival, 75.4% [95% confidence interval {CI}, 71.3 to 78.9] vs. 61.0% [95% CI, 56.5 to 65.1]; hazard ratio for recurrence or death, 0.57; 98.4% CI, 0.43 to 0.74; P < 0.001) and in the subgroup of 853 patients with PD-L1-positive tumors (1-year rate of recurrence-free survival, 77.1% [95% CI, 72.7 to 80.9] in the pembrolizumab group and 62.6% [95% CI, 57.7 to 67.0] in the placebo group; hazard ratio, 0.54; 95% CI, 0.42 to 0.69; P < 0.001). Adverse events of grades 3 to 5 that were related to the trial regimen were reported in 14.7% of the patients in the pembrolizumab group and in 3.4% of patients in the placebo group. There was one treatment-related death due to myositis in the pembrolizumab group.CONCLUSIONSAs adjuvant therapy for high-risk stage III melanoma, 200 mg of pembrolizumab administered every 3 weeks for up to 1 year resulted in significantly longer recurrence-free survival than placebo, with no new toxic effects identified.