Once patients stop responding to platinum-based chemotherapy for locally advanced or metastatic urothelial cancer, their treatment options had been somewhat limited: PD-1/PD-L1 inhibitors were effective in only 13%–29% of patients and taxanes in only 11%–13%. When the antibody drug conjugate enfortumab vedotin (EV) was approved in late 2019, it offered new hope for patients and providers, with clinical trials reporting a 44% objective response rate.

As a monoclonal antibody targeted therapy, EV is associated with unique adverse events that oncology nurses must manage. In their article in the March 2021 issue of the Clinical Journal of Oncology Nursing, Pace et al. provided a complete overview for oncology nurses caring for patients receiving EV therapy, including practical considerations and recommendations for common and potentially treatment-limiting adverse events.

Common Adverse Events With EV

The most common adverse events reported during EV’s clinical trials were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), diarrhea (42%), dysgeusia (42%), dry eyes (40%), dry skin (26%), pruritis (26%), and vomiting (18%), Pace et al. said, but “the 16% treatment discontinuation rate related to adverse events, which is consistent with other therapies in this population, suggests that the events were generally manageable.”

Oncology nurses must educate patients and caregivers about the potential for developing adverse events and when to report experiencing symptoms, Pace et al. said. They should have ongoing discussions with patients and caregivers during each weekly infusion visit and conduct regular physical exams and lab assessments. Careful monitoring and prompt intervention help patients stay on treatment and achieve the best outcomes.

Management Strategies for EV Adverse Events

Pace et al. outlined oncology nursing management strategies for skin reactions, peripheral neuropathy, ocular disorders, hyperglycemia, and gastrointestinal and hematologic toxicities from EV therapy.

Skin reactions: EV works by targeting Nectin-4 in tumor cells, but the molecule is also found in healthy skin tissue, so skin reactions are a common adverse event during therapy, with 26% of patients experiencing maculopapular rash and 30% pruritus, including 10% with grade 3–4 reactions (e.g., symmetrical drug-related intertriginous and flexural exanthema, bullous dermatitis, exfoliative dermatitis, palmar-plantar erythrodysesthesia). Most skin reactions develop within the first few weeks of the first treatment cycle, Pace et al. said.

Patients should practice good skincare as prevention (i.e., SPF 30 or higher sunscreen, lukewarm rather than hot showers, proper hydration, emollients, mild detergents and skin cleansers, alcohol- and fragrance-free hypoallergenic moisturizers, and hypoallergenic makeup). Early intervention produces the best outcomes, because dose interruption, reduction, or permanent discontinuation are recommended for grade 3–4 skin reactions.

Topical or systemic corticosteroids may be used, as well as topical antibiotics or antifungals if patients develop an associated skin infection. Assess the rash at each treatment visit and refer patients to dermatology as indicated, particularly for rashes that cover more than 30% of body surfaces; involve the mucosa, bullous lesions, or exfoliation; or do not respond to a combination of steroids, antihistamines, and dose modifications.

Peripheral neuropathy: Sensory peripheral neuropathy (i.e., pain or burning, numbness, tingling, or loss of sensation) is more common (44%) than motor peripheral neuropathy (i.e., loss of coordination or muscle weakness) (14%) and usually develops within the first three months of treatment. Patients with comorbidities (e.g., diabetes mellitus), older age, spinal metastasis, and nonmalignant spinal disease are more likely to experience the adverse event, Pace et al. said.

Even more so than for other adverse events, early identification is critical for best outcomes, and Pace et al. provided a checklist for nurses to use to assess extent and severity. The only intervention is dose interruption or discontinuation; in many cases patients can resume EV therapy after peripheral neuropathy resolves or improves to grade 1, but permanent discontinuation is necessary for grade 3 or higher.

Ocular toxicities: Most ocular events involved dry eyes, including blurred vision, keratitis, and limbal stem cell deficiency, with 36% of patients experiencing dry eyes and 14% blurred vision, usually within the first two months of treatment, Pace et al. reported. The symptoms were more common in older patients and contact lens wearers.

Grade 3 or lower toxicities can be managed with artificial tears or ophthalmic topical steroids, but dose interruption or discontinuation is required for grade 3–4 ocular events. Although regular EV-related ocular exams are not required, patients should inform their eye care practitioner about their treatment, and referral to optometry or ophthalmology may help patients manage persistent symptoms.

Hyperglycemia: Treatment-related hyperglycemia occurs within the first few weeks in 11% of patients overall, including 32% with and 8% without preexisting hyperglycemia, Pace et al. said. Some of the risk factors include comorbid diabetes mellitus, illness, or infection; use of systemic steroids; and higher body mass index and baseline hemoglobin A1C.

Test patients’ blood glucose prior to each EV dose, and ensure that those with preexisting diabetes or hyperglycemia continue to see their endocrinologist and inform them of their EV treatment. If patients are hyperglycemic during EV administration, follow your institutional standard of care, including antihyperglycemic medication and consideration of referral to endocrinology. Withhold EV for nonfasting blood glucose greater than 250 mg/dl until it lowers, then resume at the same dose level.

Gastrointestinal events: Patients may experience nausea, diarrhea, vomiting, appetite loss, and dysgeusia, Pace et al. said, and cautioned oncology nurses to monitor nutritional and hydration status. EV dose modification may be necessary to prevent renal dysfunction, functional decline, fluid-electrolyte imbalance, and fatigue.

For dysgeusia, have patients try using lemon juice and chewing gum prior to meals; eating small, frequent meals; maintaining good oral hygiene; drinking water with meals; using plastic instead of metal utensils; applying more or less salt and flavoring for food; and avoiding foods with strong smells. ONS offers a plethora of nutrition resources.

Hematologic events: Less than 10% of patients developed grade 3-4 hematologic toxicities in clinical trials, but managing them is critical. Dose interruption, reduction, or permanent discontinuation is recommended for grade 3–4 hematologic laboratory abnormalities or grade 2 or greater thrombocytopenia. Monitor patients’ labs regularly for neutropenia, anemia, and thrombocytopenia.

For more information about managing adverse events from EV therapy, refer to the full article by Pace et al.