Department of Urology, University Hospital of Brussels, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium -
Department of Oncology, University Hospital of Brussels, Erasme Hospital and Jules Bordet Institute, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Minerva Urol Nephrol. 2021 Jun;73(3):292-298. doi: 10.23736/S2724-6051.21.04309-5. Epub 2021 Mar 29.
High risk non-muscle invasive bladder cancer (NMIBC) is a recurring and potentially lethal disease. To date, with the exception of radical surgery, there are no validated strategies for patients not responding to intravesical BCG therapy. Immune checkpoint inhibitors (ICI) are currently being tested for BCG-resistant NMIBC. We report current available data and ongoing trials exploring the efficacy and safety of ICI in this setting.
A narrative search was performed including the combination of the following words: ("immunotherapy") AND ("BCG" AND "resistant" OR "non-muscle AND invasive") AND ("bladder AND "cancer"). Three search engines: PubMed, Embase and Web of Science were queried up to November 1, 2020. Congress abstracts reporting results and not only trials' design were also referenced. The US National Library of Medicine was queried via clinicaltrials.gov to explore ongoing trials on the subject.
Pembrolizumab demonstrated a promising 40.6% (95% CI: 30.7-51.1) complete response within the KEYNOTE-057, with a median duration of response of 16.2 months. Preliminary data in the phase II SWOG S1605 trial with atezolizumab showed a 41.1% complete response at 3 months. Avelumab is being tested in the PREVERT phase II study exploring ICI with radiotherapy (60-66 Gy) of the whole bladder. CheckMate 9UT analyzes nivolumab monotherapy versus nivolumab + BMS-986205 (IDO-1 inhibitor) with or without BCG in patients with BCG-unresponsive, carcinoma in situ with or without papillary component. Finally, durvalumab is being studied in the BCG resistant space with radiotherapy in the ADAPT-BLADDER study. After proving its safety profile in the phase 1, the trial will randomize patients to durvalumab + BCG, durvalumab + radiation therapy (6Gy 3×) or BCG rechallenge.
Pembrolizumab has received FDA approval in the treatment of BCG-resistant NMIBC. All five other ICI molecules are currently being extensively tested within clinical trials. The results of the currently ongoing studies are awaited with impatience by the uro-oncologic community and will probably open a new era in the treatment of BCG-resistant NMIBC.
高危非肌肉浸润性膀胱癌（NMIBC）是一种复发性且潜在致命的疾病。迄今为止，除根治性手术外，对于卡介苗（BCG）治疗无反应的患者，尚无经证实的治疗策略。免疫检查点抑制剂（ICI）目前正在用于治疗 BCG 耐药性 NMIBC。我们报告了当前可用的数据和正在进行的试验，以探索 ICI 在该环境中的疗效和安全性。
进行了叙述性搜索，包括以下单词的组合：（“免疫疗法”）和（“BCG”和“耐药”或“非肌肉”和“浸润”）和（“膀胱”和“癌症”）。使用了三个搜索引擎：PubMed、Embase 和 Web of Science 进行了查询，截至 2020 年 11 月 1 日。还参考了报告结果的会议摘要，而不仅仅是试验设计。通过美国国立医学图书馆在 clinicaltrials.gov 上查询，以探索该主题的正在进行的试验。
在 KEYNOTE-057 中，帕博利珠单抗显示出有希望的 40.6%（95%CI：30.7-51.1）完全缓解率，中位缓解持续时间为 16.2 个月。在 II 期 SWOG S1605 试验中使用阿替利珠单抗的初步数据显示，3 个月时完全缓解率为 41.1%。avelumab 正在 PREVERT 二期研究中进行测试，该研究探索了整个膀胱的 ICI 联合放疗（60-66Gy）。CheckMate 9UT 分析了nivolumab 单药治疗与 nivolumab+ BMS-986205（IDO-1 抑制剂）联合或不联合 BCG 在无 BCG 反应、原位癌伴或不伴乳头状成分的患者中的疗效。最后，durvalumab 正在 ADAPT-BLADDER 研究中与放疗联合用于 BCG 耐药性膀胱癌的研究中。在证明其安全性后，该试验将随机分配患者接受 durvalumab+BCG、durvalumab+放疗（6Gy 3×）或 BCG 再挑战。
帕博利珠单抗已获得 FDA 批准用于治疗 BCG 耐药性 NMIBC。目前其他五种 ICI 分子都正在临床试验中进行广泛测试。目前正在进行的研究结果正受到泌尿科肿瘤学界的热切期待，这可能会开创 BCG 耐药性 NMIBC 治疗的新纪元。
