Department of Urology, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa, Japan.
Department of Neurological Intractable Disease Research, Kagawa University School of Medicine, Kita, Japan.
Int J Clin Oncol. 2024 May;29(5):602-611. doi: 10.1007/s10147-024-02481-8. Epub 2024 Feb 28.
Enfortumab vedotin is a novel antibody-drug conjugate used as a third-line therapy for the treatment of urothelial cancer. We aimed to elucidate the effect of enfortumab vedotin-related peripheral neuropathy on its efficacy and whether enfortumab vedotin-induced early electrophysiological changes could be associated with peripheral neuropathy onset.
Our prospective multicenter cohort study enrolled 34 patients with prior platinum-containing chemotherapy and programmed cell death protein 1/ligand 1 inhibitor-resistant advanced urothelial carcinoma and received enfortumab vedotin. The best overall response, progression-free survival, overall survival, and safety were assessed. Nerve conduction studies were also performed in 11 patients.
The confirmed overall response rate and disease control rate were 52.9% and 73.5%, respectively. The median overall progression-free survival and overall survival were 6.9 and 13.5 months, respectively, during a median follow-up of 8.6 months. The patients with disease control had significantly longer treatment continuation and overall survival than did those with uncontrolled disease. Peripheral neuropathy occurred in 12.5% of the patients. The overall response and disease control rates were 83.3% and 100%, respectively: higher than those in patients without peripheral neuropathy (p = 0.028 and p = 0.029, respectively). Nerve conduction studies indicated that enfortumab vedotin reduced nerve conduction velocity more markedly in sensory nerves than in motor nerves and the lower limbs than in the upper limbs, with the sural nerve being the most affected in the patients who developed peripheral neuropathy (p = 0.011).
Our results indicated the importance of focusing on enfortumab vedotin-induced neuropathy of the sural nerve to maximize efficacy and improve safety.
依维莫司丁是一种新型抗体药物偶联物，被用作治疗尿路上皮癌的三线治疗药物。我们旨在阐明依维莫司丁相关周围神经病变对其疗效的影响，以及依维莫司丁诱导的早期电生理变化是否与周围神经病的发生有关。
我们的前瞻性多中心队列研究纳入了 34 名接受过含铂化疗和程序性死亡蛋白 1/配体 1 抑制剂耐药的晚期尿路上皮癌患者，并接受了依维莫司丁治疗。评估了最佳总体反应、无进展生存期、总生存期和安全性。还对 11 名患者进行了神经传导研究。
确认的总体反应率和疾病控制率分别为 52.9%和 73.5%。中位总无进展生存期和总生存期分别为 6.9 和 13.5 个月，中位随访时间为 8.6 个月。疾病控制的患者的治疗持续时间和总生存期明显长于未控制疾病的患者。12.5%的患者发生周围神经病。总体反应率和疾病控制率分别为 83.3%和 100%：高于无周围神经病的患者（p=0.028 和 p=0.029）。神经传导研究表明，依维莫司丁在感觉神经中的神经传导速度比运动神经中的降低更为明显，下肢比上肢更为明显，在发生周围神经病的患者中，腓肠神经受影响最大（p=0.011）。
我们的结果表明，关注依维莫司丁诱导的腓肠神经病变对于最大限度地提高疗效和提高安全性非常重要。
