Targeted Molecular Therapeutics for Bladder Cancer-A New Option beyond the Mixed Fortunes of Immune Checkpoint Inhibitors?
Targeted Molecular Therapeutics for Bladder Cancer-A New Option beyond the Mixed Fortunes of Immune Checkpoint Inhibitors?
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DOI：
10.3390/ijms21197268
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发表时间：
2020-10-01
影响因子：
5.6
通讯作者：
Leyton JV
中科院分区：
文献类型：
--
作者：
Bednova O;Leyton JV
事实上，自2016年以来，已有五种免疫检查点抑制剂（ICI）单克隆抗体获批，靶向程序性细胞死亡蛋白1或程序性死亡配体-1治疗转移性和难治性膀胱癌，这是一项杰出的成就。虽然患者在接受ICI治疗时可以表现出延长生存期的明显反应，但与传统化疗相比，这些药物的主要益处是它们具有更好的耐受性并导致不良事件（AE）减少。不幸的是，ICI治疗的反应率相对较低，这些药物价格昂贵，经济负担高。因此，其临床疗效/成本-价值关系存在争议。长期以来一直寻求的靶向分子治疗现在已经出现，并且在大量预治疗（包括ICI治疗）的转移性膀胱癌患者中具有令人印象深刻的反应率。已证明抗体-药物缀合物（ADC）恩福妥单抗（EV）和萨希珠单抗（SG）在表达Nectin-4和Trop-2的膀胱肿瘤细胞患者中分别提供44%和31%的客观缓解率（ORR）的能力。因此，EV被美国食品和药物管理局批准用于治疗先前接受过ICI和含铂化疗的晚期或转移性膀胱癌患者。SG已被授予快速通道指定。小分子Erdafitinib最近被批准用于治疗晚期或转移性膀胱癌患者，这些患者的成纤维细胞生长因子受体发生遗传改变，这些患者先前曾接受过含铂化疗。Erdafitinib在包括部分既往接受ICI治疗的患者中实现了40%的ORR。此外，这些靶向药物具有足够的耐受性，或者可以适当管理AE。因此，这些靶向药物的临床有效性的早期表现相对于ICI大幅增加。在本文中，描述了ICI和靶向治疗的治疗疗效和AE的最新随访。此外，药品价格和成本效益进行了描述。考虑到临床有效性、价格和成本效益的最佳总体价值，结果有利于avelumab和atezolizumab用于ICI。虽然在治疗上有希望，但确定所描述的靶向治疗是否提供最佳的整体价值还为时过早，因为尚未进行成本效益分析，需要长期随访。尽管如此，随着靶向分子治疗剂的到来及其相对于ICI的有效性增加，创造了一种基于“靶向”的潜在新范例，用于影响转移性膀胱癌治疗的临床实践。
The fact that there are now five immune checkpoint inhibitor (ICI) monoclonal antibodies approved since 2016 that target programmed cell death protein 1 or programmed death ligand-1 for the treatment of metastatic and refractory bladder cancer is an outstanding achievement. Although patients can display pronounced responses that extend survival when treated with ICIs, the main benefit of these drugs compared to traditional chemotherapy is that they are better tolerated and result in reduced adverse events (AEs). Unfortunately, response rates to ICI treatment are relatively low and, these drugs are expensive and have a high economic burden. As a result, their clinical efficacy/cost-value relationship is debated. Long sought after targeted molecular therapeutics have now emerged and are boasting impressive response rates in heavily pre-treated, including ICI treated, patients with metastatic bladder cancer. The antibody-drug conjugates (ADCs) enfortumab vedotin (EV) and sacituzumab govitecan (SG) have demonstrated the ability to provide objective response rates (ORRs) of 44% and 31% in patients with bladder tumor cells that express Nectin-4 and Trop-2, respectively. As a result, EV was approved by the U.S. Food and Drug Administration for the treatment of patients with advanced or metastatic bladder cancer who have previously received ICI and platinum-containing chemotherapy. SG has been granted fast track designation. The small molecule Erdafitinib was recently approved for the treatment of patients with advanced or metastatic bladder cancer with genetic alterations in fibroblast growth factor receptors that have previously been treated with a platinum-containing chemotherapy. Erdafitinib achieved an ORR of 40% in patients including a proportion who had previously received ICI therapy. In addition, these targeted drugs are sufficiently tolerated or AEs can be appropriately managed. Hence, the early performance in clinical effectiveness of these targeted drugs are substantially increased relative to ICIs. In this article, the most up to date follow-ups on treatment efficacy and AEs of the ICIs and targeted therapeutics are described. In addition, drug price and cost-effectiveness are described. For best overall value taking into account clinical effectiveness, price and cost-effectiveness, results favor avelumab and atezolizumab for ICIs. Although therapeutically promising, it is too early to determine if the described targeted therapeutics provide the best overall value as cost-effectiveness analyses have yet to be performed and long-term follow-ups are needed. Nonetheless, with the arrival of targeted molecular therapeutics and their increased effectiveness relative to ICIs, creates a potential novel paradigm based on ‘targeting’ for affecting clinical practice for metastatic bladder cancer treatment.
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影响因子：
8.8
作者：
Jenkins RW;Barbie DA;Flaherty KT
通讯作者：
Flaherty KT
影响因子：
45.3
作者：
Hussain, Maha H. A.;MacVicar, Gary R.;Smith, David C.
通讯作者：
Smith, David C.
影响因子：
45.3
作者：
Bardia, Aditya;Mayer, Ingrid A.;Vahdat, Linda T.
通讯作者：
Vahdat, Linda T.
DOI：
10.1158/1078-0432.ccr-19-4162
发表时间：
2020-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Galsky MD;Saci A;Szabo PM;Han GC;Grossfeld G;Collette S;Siefker-Radtke A;Necchi A;Sharma P
通讯作者：
Sharma P
影响因子：
45.3
作者：
De Santis, Maria;Bellmunt, Joaquim;Sylvester, Richard
通讯作者：
Sylvester, Richard