Abstract
Background
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.
Methods
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.
Results
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).
Conclusion
Our results indicated the importance of focusing on enfortumab vedotin-induced neuropathy of the sural nerve to maximize efficacy and improve safety.
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Data availability
The data supporting the findings in this study are available within the paper, in the corresponding Online Resource, or upon reasonable request from the corresponding author.
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Acknowledgements
The authors thank the patients and their families who were involved in this post-marketing survey and the physicians who cooperated with the survey and data collection.
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This study did not receive any specific grants from funding agencies in the public, commercial, or non-profit sectors.
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Online Resource 1
The objective response and outcome of EV treatment in the patients with and without peripheral neuropathy. Supplementary file1 (JPG 103 KB)
Appendix
Appendix
Study institutes: Kagawa University, Takamatsu Red Cross Hospital, Kagawa Prefectural Central Hospital, Tokushima University Graduate School of Biomedical Sciences, Sakaide City Hospital, Mitoyo General Hospital, Shodoshima Central Hospital, Kansai Medical University, Kyoto University Graduate School of Medicine and KKR Takamatsu Hospital.
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Taoka, R., Kamada, M., Izumi, K. et al. Peripheral neuropathy and nerve electrophysiological changes with enfortumab vedotin in patients with advanced urothelial carcinoma: a prospective multicenter cohort study. Int J Clin Oncol 29, 602–611 (2024). https://doi.org/10.1007/s10147-024-02481-8
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DOI: https://doi.org/10.1007/s10147-024-02481-8