Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma
Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma
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DOI：
10.1056/nejmoa2002788
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发表时间：
2020-09-24
影响因子：
158.5
通讯作者：
Grivas, Petros
中科院分区：
文献类型：
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作者：
Powles, Thomas;Park, Se Hoon;Grivas, Petros
背景：铂类化疗是晚期尿路上皮癌的一线治疗标准。然而，无进展生存期和总生存期受到化疗耐药的限制。方法：在一项3期试验中，我们随机分配了一线化疗（4 - 6个周期吉西他滨加顺铂或卡铂）没有疾病进展的不可切除的局部晚期或转移性尿路上皮癌患者，接受最佳支持治疗，或不接受维持阿维单抗。主要终点是总生存率，在所有接受随机分组的患者（总体人群）和程序性细胞死亡配体1 （PD-L1）阳性肿瘤患者中进行评估。次要终点包括无进展生存期和安全性。结果：在所有接受随机分组的700名患者中，与单独接受最佳支持治疗相比，在最佳支持治疗中加入维持性avelumab显著延长了总生存期（对照组）。avelumab组1年总生存率为71.3%，对照组为58.4%（中位总生存率为21.4个月vs 14.3个月；死亡风险比为0.69；95%可信区间[CI]， 0.56 ~ 0.86； P=0.001）。Avelumab还显著延长pd - l1阳性人群的总生存期；阿韦单抗组1年总生存率为79.1%，对照组为60.4%(风险比0.56;95% CI, 0.40 ~ 0.79； P
BACKGROUNDPlatinum-based chemotherapy is standard-of-care first-line treatment for advanced urothelial carcinoma. However, progression-free survival and overall survival are limited by chemotherapy resistance.METHODSIn a phase 3 trial, we randomly assigned patients with unresectable locally advanced or metastatic urothelial cancer who did not have disease progression with first-line chemotherapy (four to six cycles of gemcitabine plus cisplatin or carboplatin) to receive best supportive care with or without maintenance avelumab. The primary end point was overall survival, assessed among all patients who underwent randomization (overall population) and among those with tumors positive for programmed cell death ligand 1 (PD-L1). Secondary end points included progression-free survival and safety.RESULTSAmong all 700 patients who underwent randomization, the addition of maintenance avelumab to best supportive care significantly prolonged overall survival as compared with best supportive care alone (control). Overall survival at 1 year was 71.3% in the avelumab group and 58.4% in the control group (median overall survival, 21.4 months vs. 14.3 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.86; P=0.001). Avelumab also significantly prolonged overall survival in the PD-L1-positive population; overall survival at 1 year was 79.1% in the avelumab group and 60.4% in the control group (hazard ratio, 0.56; 95% CI, 0.40 to 0.79; P