From the FDA Drug Label
Serious adverse reactions in ≥2% of patients receiving KEYTRUDA in combination with enfortumab vedotin were rash (6%), acute kidney injury (5%), pneumonitis/ILD (4.5%), urinary tract infection (3.6%), diarrhea (3.2%), pneumonia (2. 3%), pyrexia (2%), and hyperglycemia (2%). Serious adverse reactions in ≥2% of patients receiving KEYTRUDA in combination with enfortumab vedotin were acute kidney injury (7%), urinary tract infection (7%), urosepsis (5%), hematuria (3.3%), pneumonia (3.3%), pneumonitis (3.3%), sepsis (3. 3%), anemia (2.5%), diarrhea (2.5%), hypotension (2.5%), myasthenia gravis (2.5%), myositis (2.5%), and urinary retention (2.5%).
The urinary tract infection is a serious adverse reaction that occurred in patients receiving EV+Pembrolizumab. However, the label does not provide guidance on whether to hold EV+Pembrolizumab in the event of a urinary tract infection.
- The decision to hold EV+Pembrolizumab should be based on clinical judgment, considering the severity of the infection and the patient's overall condition.
- In general, it is recommended to hold or interrupt treatment with immunotherapy in cases of severe or grade 3/4 adverse reactions, until the reaction resolves or improves to grade 1 1.
From the Research
Yes, EV (enfortumab vedotin) plus pembrolizumab should typically be held during an active urinary tract infection (UTI). Treatment should be paused until the infection resolves and antibiotics are completed. The patient should be afebrile for at least 24-48 hours with normalized or improving laboratory values before resuming therapy. This recommendation is based on several factors, including the potential for immunotherapy with pembrolizumab to impair the immune response needed to fight infections, as seen in a study where antibiotic use was negatively associated with outcomes in patients with metastatic urothelial carcinoma who were administered pembrolizumab 2.
Key Considerations
- Immunotherapy with pembrolizumab can impair the immune response needed to fight infections
- The additional stress of chemotherapy with EV could further compromise the patient's ability to clear the infection
- Treating through an active infection may increase the risk of sepsis or other serious complications
- The use of antibiotics, such as nitrofurantoin, can be effective in treating UTIs, but may also have an impact on the efficacy of pembrolizumab 3, 4, 5
Management Approach
- Pause EV plus pembrolizumab treatment until the UTI is resolved
- Complete a course of antibiotics as prescribed by a healthcare provider
- Monitor the patient's condition closely and reassess before restarting therapy
- Maintain adequate hydration both during the infection and upon resumption of therapy
- Be aware of the potential for urinary tract symptoms to represent immune-related adverse events from pembrolizumab 2