Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Greenberg Bladder Cancer Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Eur Urol. 2022 Feb;81(2):138-142. doi: 10.1016/j.eururo.2021.10.009. Epub 2021 Nov 1.
The treatment landscape for advanced urothelial cancer has changed dramatically owing to the US Food and Drug Administration approval and introduction of antibody-drug conjugates (ADCs), including enfortumab vedotin and sacituzumab govitecan. Efforts have begun to use these therapies in earlier disease states, specifically bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC). We assessed gene expression associated with these newly approved therapies in a novel cohort of treatment-naïve NMIBC tumors before and after BCG therapy. Multiple genes, including Nectin-4, Trop-2, and Her-2, exhibited increased expression after BCG therapy compared to baseline. However, few of the tumors with increased expression of ADC targets also exhibited increased PD-L1/PD-1 expression. Taken together, these data demonstrate the heterogeneous genomic landscape of BCG-exposed NMIBC, and provide evidence supporting the evaluation of ADCs in NMIBC. PATIENT SUMMARY: We evaluated the potential role of targeted therapies that have been approved in the USA for advanced non-muscle-invasive bladder cancer (NMIBC) that has recurred after treatment with bacillus Calmette-Guérin (BCG). By assessing levels of specific genes and proteins linked to the targeted therapies, we demonstrate that there is rationale for further evaluation of these therapies in NMIBC.
由于美国食品和药物管理局批准并推出了抗体药物偶联物（ADC），包括恩福妥珠单抗和Sacituzumab govitecan，晚期尿路上皮癌的治疗格局发生了巨大变化。人们已经开始在早期疾病状态下使用这些疗法，特别是卡介苗（BCG）无反应性非肌肉浸润性膀胱癌（NMIBC）。我们在一组新的未经治疗的 NMIBC 肿瘤中评估了与这些新批准的疗法相关的基因表达，这些肿瘤在 BCG 治疗前后均处于治疗前状态。与基线相比，BCG 治疗后有多个基因（包括 Nectin-4、Trop-2 和 Her-2）表达增加。然而，在 ADC 靶点表达增加的肿瘤中，很少有 PD-L1/PD-1 表达增加。总之，这些数据表明 BCG 暴露的 NMIBC 具有异质性的基因组景观，并为在 NMIBC 中评估 ADC 提供了证据支持。患者总结：我们评估了在美国已被批准用于治疗卡介苗（BCG）治疗后复发的晚期非肌肉浸润性膀胱癌（NMIBC）的靶向治疗的潜在作用。通过评估与靶向治疗相关的特定基因和蛋白的水平，我们证明了在 NMIBC 中进一步评估这些治疗方法的合理性。
