Gopalakrishnan Dharmesh, Koshkin Vadim S, Ornstein Moshe C, Papatsoris Athanasios, Grivas Petros
Department of Hospital Medicine, Cleveland Clinic, Cleveland, OH, USA.
Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH, USA.
Ther Clin Risk Manag. 2018 Jun 5;14:1019-1040. doi: 10.2147/TCRM.S158753. eCollection 2018.
Bladder cancer is the sixth most common cancer in the US and most tumors have urothelial (transitional cell) histology. Platinum-based chemotherapy has long been the standard of care in advanced disease, but long-term outcomes have largely remained poor. Since the peak incidence of bladder cancer is in the eighth decade of life and beyond, medical comorbidities may often limit the use of chemotherapy. Immune checkpoint inhibitors with their favorable toxicity profiles and notable antitumor activity have ushered in a new era in the treatment of advanced urothelial cancer (UC) with five agents targeting the PD-1/PD-L1 pathway being recently approved by the US Food and Drug administration. A plethora of clinical trials are ongoing in diverse disease settings, employing agents targeting PD-1/PD-L1 and related immune checkpoint pathways. While reactivating anti-tumor immunity, these agents may lead to a unique constellation of immune-related adverse events, which may warrant discontinuation of therapy and potential use of immunosuppression. Novel combinations with various treatment modalities and optimal sequencing of active therapies are being investigated in prospective clinical trials and retrospective registries. At the era of precision molecular medicine, and since patients do not respond uniformly to these agents, there is a growing need for identification and validation of biomarkers that can accurately predict treatment response and assist in patient selection. This review discusses current updates and future directions of immunotherapy in advanced UC.
膀胱癌是美国第六大常见癌症，大多数肿瘤具有尿路上皮（移行细胞）组织学特征。长期以来，铂类化疗一直是晚期疾病的标准治疗方法，但长期疗效在很大程度上仍然较差。由于膀胱癌的发病率高峰在八十岁及以上人群，合并症往往会限制化疗的使用。免疫检查点抑制剂因其良好的毒性特征和显著的抗肿瘤活性，开创了晚期尿路上皮癌（UC）治疗的新时代，目前已有五种靶向PD-1/PD-L1途径的药物获得美国食品药品监督管理局批准。大量针对不同疾病背景的临床试验正在进行，这些试验使用了靶向PD-1/PD-L1及相关免疫检查点途径的药物。在激活抗肿瘤免疫的同时，这些药物可能会引发一系列独特的免疫相关不良事件，这可能需要停止治疗并可能使用免疫抑制疗法。在前瞻性临床试验和回顾性登记研究中，正在探索与各种治疗方式的新型联合用药以及活性疗法的最佳序贯方案。在精准分子医学时代，由于患者对这些药物的反应并不一致，因此越来越需要识别和验证能够准确预测治疗反应并协助患者选择的生物标志物。本综述讨论了晚期UC免疫治疗的当前进展和未来方向。
