Consensus guidance on early identification and management of peripheral neuropathy in patients with UC receiving enfortumab vedotin: A Delphi study.

Abstract

661 Background: Peripheral neuropathy (PN) is a cumulative, debilitating, and potentially dose-limiting adverse event associated with enfortumab vedotin (EV) given either as monotherapy or with pembrolizumab (P). Due to the significant activity of EV+P in muscle-invasive bladder cancer and locally advanced or metastatic urothelial carcinoma (la/mUC), early identification and management of PN is a critical part of optimizing patient outcomes on EV+/-P. This study aims to develop consensus on best practices for early dentification and management of EV-associated PN, including how to counsel patients initiating EV and their caregivers on short/long-term PN monitoring. Methods: A RAND/UCLA modified Delphi panel included US-based, multidisciplinary healthcare professionals experienced in managing PN in patients with la/mUC treated with EV. A rating form (survey) informed by a targeted literature review (TLR) and individual expert interviews presented hypothetical patient scenarios and potential strategies for early identification, management of EV-associated PN, and counselling patients initiating EV and their caregivers on PN monitoring. Panellists independently rated strategy appropriateness using a 1–9 scale before and after an in-person meeting. Second-round ratings were analyzed using the RAND/UCLA Appropriateness Method to develop consensus-based clinical guidance. The Delphi panel is ongoing, and results will be reported at the time of presentation. Results: Here we present the findings of the TLR, which included 46 studies. Assessing PN is challenging as patients may underreport symptoms due to fear of treatment interruption, clinicians can underestimate symptom severity, and patient-reported outcomes may not correlate with objective findings. Functional assessments and screening questions at each treatment cycle can aid identification, while sensory assessments are performed selectively. There are no consensus guidelines for EV-associated PN. Dose modification is the primary management strategy, but evidence on outcomes after early intervention following PN emergence is limited. Pharmacologic interventions may be effective at reducing chemotherapy-induced neuropathic pain depending on whether the patient exhibits positive and/or negative PN-symptoms. Multidisciplinary approaches, including education or physical/occupational therapy may be beneficial. Conclusions: Early assessment, detection and proactive intervention are critical to improving outcomes in EV-associated PN in patients with UC. There are opportunities to further develop, educate and advance guideline-driven management of EV-associated PN. This ongoing Delphi study will provide the first expert consensus to guide clinical decision-making and address gaps in managing EV-associated PN in patients with UC.