Enfortumab Vedotin-Induced Peripheral Neuropathy Management

Evidence for Reversibility

• Grade 1-2 peripheral neuropathy occurs in 56.4% of patients treated with enfortumab vedotin plus pembrolizumab, while grade 3 neuropathy occurs in 6.8% 1
• Patients with pre-existing neuropathy or grade ≥2 neuropathy are typically excluded from enfortumab vedotin treatment eligibility 2, 3

Clinical Course After Discontinuation

• A "coasting phenomenon" may occur where neuropathy symptoms can worsen for 2-3 months after treatment cessation before improvement begins, similar to oxaliplatin-induced neuropathy 4
• Complete resolution is not guaranteed, particularly in patients who developed severe (grade 3+) neuropathy during treatment 5, 6

Management Strategy During Treatment

• Baseline neurological evaluation is essential before initiating enfortumab vedotin, with monitoring before each treatment cycle 4

Treatment of Established Neuropathy

• Duloxetine is the only agent with strong evidence for treating chemotherapy-induced peripheral neuropathy and should be offered as first-line treatment 4, 5, 6
• Gabapentin or pregabalin serve as reasonable alternatives for neuropathic pain management 4
• Tricyclic antidepressants (nortriptyline or desipramine) may be considered despite limited specific evidence for chemotherapy-induced neuropathy 5, 6

Critical Caveats

• Permanent neuropathy can occur, particularly with cumulative dosing or delayed intervention 4
• Risk factors that worsen prognosis include pre-existing diabetes, renal insufficiency, vitamin deficiencies, and concurrent neurotoxic medications 4