Nykopp Timo K, Batista da Costa Jose, Mannas Miles, Black Peter C
Department of Surgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Level 6, 2775 Laurel St, Vancouver, BC, V6N 2W6, Canada.
Curr Urol Rep. 2018 Oct 24;19(12):101. doi: 10.1007/s11934-018-0852-6.
As our molecular understanding of bladder cancer continues to advance, more and more novel agents are entering clinical trials across the spectrum of bladder cancer stages. The clinical trial activity for non-muscle invasive bladder cancer (NMIBC) has been boosted further by the evolution of specific disease states that set more uniform inclusion criteria for clinical trial design. Here, we aimed to review the current clinical trials landscape in non-muscle invasive bladder cancer with respect to these disease states.
Most active clinical trials focus on high-risk NMIBC in either the BCG-naïve or BCG-unresponsive setting. Strict criteria to define the disease state and a clear pathway to drug registration have encouraged trials for patients with BCG-unresponsive NMIBC. The most promising potential breakthroughs for BCG-naïve patients include alternative BCG strains, immune-priming with intradermal BCG vaccination, and systemic immune checkpoint blockade. The latter therapy is also being actively investigated in multiple trials in BCG-unresponsive NMIBC, along with novel viral agents such as INSTILADRIN (nadofaragene firadenovec) and targeted agents such as oportuzumab monatox. After many years of relative stagnation, multiple new therapies currently under investigation in well-designed clinical trials appear poised for routine clinical implementation in the near future. These therapies should dramatically improve the outcome of patients with NMIBC. We can look forward to the challenges of biomarker-driven drug selection, optimal drug sequencing, and rational combination therapies.
随着我们对膀胱癌分子层面的理解不断深入，越来越多的新型药物正进入针对各个膀胱癌阶段的临床试验。非肌肉浸润性膀胱癌（NMIBC）特定疾病状态的演变进一步推动了临床试验活动，这些疾病状态为临床试验设计设定了更统一的纳入标准。在此，我们旨在就这些疾病状态综述非肌肉浸润性膀胱癌当前的临床试验情况。
大多数活跃的临床试验聚焦于初治卡介苗（BCG）或卡介苗无反应情况下的高危NMIBC。定义疾病状态的严格标准以及明确的药物注册途径鼓励了针对卡介苗无反应性NMIBC患者的试验。对于初治卡介苗患者，最有前景的潜在突破包括替代卡介苗菌株、皮内卡介苗接种的免疫启动以及全身性免疫检查点阻断。后一种疗法也正在卡介苗无反应性NMIBC的多项试验中积极研究，同时还有新型病毒制剂如INSTILADRIN（纳多福韦基因腺病毒载体）和靶向制剂如oportuzumab monatox。经过多年的相对停滞，目前在精心设计的临床试验中研究的多种新疗法似乎在不久的将来有望常规临床应用。这些疗法应能显著改善NMIBC患者的预后。我们期待生物标志物驱动的药物选择、最佳药物序贯以及合理联合治疗方面的挑战。
