晚期尿路上皮癌中针对PD-1/PD-L1的免疫治疗研究进展

Research progress in immunotherapy against PD-1/PD-L1 for advanced urothelial carcinoma

对晚期尿路上皮癌患者采用以铂类为基础的化疗治疗效果欠佳,近来应用免疫检查点抑制剂为患者的治疗带来了新的希望。自2016年5月起,5种针对PD-1/PD-L1通路(Atezolizumab,Pembrolizumab,Nivolumab,Avelumab和Durvalumab)的药物已获得FDA批准用于治疗铂耐药的晚期尿路上皮癌,其中Pembrolizumab和Atezolizumab是上述治疗中的一线用药。这些药物的临床疗效和安全性在不同试验中的结果相似,但目前仅Pembrolizumab得到大样本随机Ⅲ期临床试验Ⅰ级结果的支持。结果表明,在铂类耐药情况下,相比传统补救性化疗,Pembrolizumab更能使患者总体生存获益。Pembrolizuma在铂类耐药晚期尿路上皮癌患者的治疗中疗效最佳,而Pembrolizumab和Atezolizumab在顺铂无效患者的临床应用中具有相近的疗效。

Cisplatin-based chemotherapy is not effective in patients with advanced urothelial carcinoma. Recently, the application of immunological checkpoint inhibitors has brought new insight to resolve this problem. Since May 2016, five drugs, including Atezolizumab, Pembrolizumab, Nivolumab, Avelumab, and Durvalumab, targeting the PD-1/PD-L1 pathway have been approved by the FDA for the treatment of cisplatin-ineligible patients with advanced urothelial carcinoma, of which Pembrolizumab and Atezolizumab are the first-line drugs in the above treatments. The clinical efficacy and safety of these drugs are similar in different trials, but only Pembrolizumab is supported by a current level I evidence from a large randomized phase clinical trials. The results show that in the case of cisplatin ineligibility, Pembrolizumab is more effective than the traditional salvage chemotherapy in overall survival rate. Pembrolizuma is most effective in the treatment of cisplatin-ineligible patients with advanced urothelial carcinoma, while Pembrolizumab and Atezolizumab have similar efficacy in clinical applications of patients with cisplatin ineffective.