《新英格兰医学杂志》2018年4月15日在线先发

http://www.nejm.org/doi/full/10.1056/NEJMoa1802357?query=featured_home

在手术切除的III期黑色素瘤中辅助派姆单抗对比安慰剂的疗效

背景

现已发现，程序性死亡1（PD-1）抑制剂派姆单抗可以延长晚期黑色素瘤患者的无进展生存期和总生存期。我们实施了一项3期双盲临床试验，以评价在手术切除的高危III期黑色素瘤患者中派姆单抗辅助治疗的效果。

方法

将完整切除的III期黑色素瘤患者随机分组（根据癌症分期和地域进行亚组分层），一组接受派姆单抗200mg，每3周静脉注射一次，共计18个剂量（大约1年）或直至肿瘤复发或出现不可耐受的毒副作用（514名）；另一组接受安慰剂（505名）。在所有意向性治疗人群中以及在PD-1配体（PD-L1）阳性的肿瘤患者亚组中的无复发生存为主要终点，还进行了安全性评估。

结果

中位随访15个月时，在所有意向性治疗人群中（1年无复发生存率，75.4%[95%置信区间{CI}，71.3-78.9]对比61.0%[95%CI，56.5-65.1]；复发或死亡的风险比，0.57，98.4%CI，0.43-0.74；P<0.001）以及在853名PD-1配体（PD-L1）阳性的肿瘤患者亚组中（1年无复发生存率，派姆单抗组77.1%[95%CI，72.7-80.9]，安慰剂组62.6%[95%CI，57.7-67.0]；风险比，0.54，95%CI，0.42-0.69；P<0.001），派姆单抗治疗比安慰剂明显延长了无复发生存期。派姆单抗组有14.7%的患者报告了与试验治疗方案相关的3-5级不良事件，安慰剂组有3.4%。派姆单抗组有一例由于肌炎引起的治疗相关性死亡。

结论

作为高危III期黑色素瘤的辅助治疗，每3周一次注射派姆单抗200mg长达1年，使得无复发生存期比安慰剂明显延长，未发现新的毒副作用。

《壹篇》南南和北北

Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma

Background

The 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.

Methods

Patients 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.

Results

At 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.

Conclusions

As 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. (Funded by Merck; ClinicalTrials.gov number, NCT02362594; EudraCT number, 2014-004944-37.)

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