Unlike immunotherapy, where re-challenge after progression is dubious, there is an emerging clinical practice of re-challenging patients with the same antibody-drug conjugate (ADC), such as enfortumab vedotin (EV), after a treatment break forced by toxicity. Anecdotally, patients are showing great responses, highlighting a key area for prospective data generation.

In the EV+pembrolizumab combination, if a patient achieves an excellent response but develops prohibitive EV-related toxicities like neuropathy, a viable strategy is to discontinue EV and maintain the patient on pembrolizumab monotherapy. This can sustain the response while improving quality of life.

A common clinical observation is that patients who develop significant immune-related toxicities, like colitis or pneumonitis, are frequently the same ones who experience the most profound and durable responses to checkpoint inhibitor therapy.

For rashes caused by enfortumab vedotin (EV), dupilumab is an emerging steroid-sparing treatment. It can decrease the risk and severity of EV-related rashes, offering an alternative to corticosteroids, which some clinicians worry may blunt the efficacy of concurrent immunotherapy.

While severe (Grade 3+) neuropathy from enfortumab vedotin is rare, oncologists emphasize that Grade 2 toxicity is common and significantly impairs patients' quality of life. This 'moderate' side effect is often painful and interferes with daily activities, warranting an immediate hold on treatment, not just waiting for Grade 3.

For patients who relapse on adjuvant nivolumab without prior immune-mediated toxicity, clinicians should consider treatment with enfortumab vedotin plus pembrolizumab. The synergy from EV's cell-killing mechanism may re-awaken the immune system, making the combination more effective than EV alone.

When a toxicity like rash occurs with EV+pembrolizumab—which could be caused by either drug—the recommended strategy is to stop both. After the rash improves, reintroduce the drug least suspected of causing it first. If the rash does not recur, it helps confirm the other agent was the culprit.

Nurses can better anticipate and educate patients about immunotherapy side effects by understanding their typical timeline. Skin and GI issues often appear within the first month, while thyroid or other endocrine problems may not manifest for two months or more.

Unlike chemotherapy, immune-related adverse events have a delayed onset. Nurses must educate patients that toxicities can appear long after treatment initiation and even after its conclusion, requiring long-term vigilance.