Teets Amanda, Pham Linda, Tran Emma Lan, Hochmuth Lana, Deshmukh Rahul
School of Pharmacy, Lake Erie College of Osteopathic Medicine, Bradenton, Florida.
Crit Rev Immunol. 2018;38(3):159-206. doi: 10.1615/CritRevImmunol.2018025204.
Long-term treatment in the setting of metastatic Merkel cell carcinoma (MCC) and urothelial carcinoma (UC) has shown that current first-line chemotherapeutic agents are losing effectiveness and that there are limited treatment options available outside of radiation therapy and surgical interventions. The use of immunotherapeutic agents such as monoclonal antibodies has been considered a promising alternative for cancers that progress despite treatment with radiation therapy, surgery, and/or chemotherapeutic agents. Cancer cells escape immune surveillance by interrupting immune checkpoint pathways, resulting in dysregulation of T-cell function and so preventing its antitumor effects. In early 2017, avelumab (BAVENCIO®), a PD-L1-blocking monoclonal antibody agent, was approved for the treatment of metastatic MCC and UC. Trials that evaluated avelumab for the treatment of metastatic MCC and UC were the JAVELIN Merkel 200 Trial and the JAVELIN Solid Tumor trial, respectively. Efficacy results for both trials showed positive overall response rate (ORR) and progression-free survival rate (PFS). A strong safety profile was also established for avelumab. This review provides a brief introduction to checkpoint inhibitors and focuses on the recently approved PD-L1 inhibitor, avelumab.
转移性默克尔细胞癌（MCC）和尿路上皮癌（UC）的长期治疗表明，当前的一线化疗药物正逐渐失去疗效，且除放射治疗和手术干预外，可用的治疗选择有限。对于那些尽管接受了放射治疗、手术和/或化疗药物治疗仍进展的癌症，使用单克隆抗体等免疫治疗药物被认为是一种有前景的替代方法。癌细胞通过中断免疫检查点通路逃避免疫监视，导致T细胞功能失调，从而阻止其抗肿瘤作用。2017年初，avelumab（BAVENCIO®），一种阻断PD-L1的单克隆抗体药物，被批准用于治疗转移性MCC和UC。评估avelumab治疗转移性MCC和UC的试验分别是JAVELIN Merkel 200试验和JAVELIN实体瘤试验。两项试验的疗效结果均显示出总体缓解率（ORR）和无进展生存率（PFS）呈阳性。avelumab也确立了良好的安全性。本综述简要介绍了检查点抑制剂，并重点关注最近获批的PD-L1抑制剂avelumab。
