Dr Park on Individualized First-Line Bladder Cancer Management Options

“It’s very important to select the right patients for each treatment.”

Chandler Park, MD, MSc, FACP, a medical oncologist at Norton Healthcare, discussed patient characteristics and disease features that influence his treatment decision-making for patients with previously untreated locally advanced or metastatic bladder cancer.

When selecting frontline treatment options for patients with bladder cancer, patient-specific factors, such as comorbidities and treatment tolerability, are critical considerations, Park began. Although enfortumab vedotin–ejfv (Padcev) plus pembrolizumab (Keytruda) is a standard regimen for the treatment of this patient population, it may not be suitable for all patients, including those with uncontrolled diabetes mellitus, he emphasized. Patients with persistently elevated glucose levels above 300 mg/dL are at risk of developing complications like diabetic ketoacidosis, as observed in the phase 3 EV-301 study (NCT03474107) that investigated enfortumab vedotin alone in patients with previously treated advanced disease, he said. Thus, strict glycemic control is essential when considering enfortumab vedotin–based therapy, he explained.

For patients who are ineligible for enfortumab vedotin plus pembrolizumab, alternative treatment regimens include cisplatin-based chemotherapy plus nivolumab (Opdivo), or the phase 3 JAVELIN-Bladder100 trial (NCT02603432) regimen, Park stated. The decision between these regimens hinges on cisplatin eligibility, which requires a creatinine clearance level above 60 mL/min, sensory neuropathy of grade 1 or lower, and the absence of significant peripheral neuropathy or severe heart failure per the New York Heart Association criteria, he noted. Patients with contraindications to cisplatin, including significant neuropathy or cardiac dysfunction, may instead receive carboplatin plus gemcitabine followed by maintenance avelumab (Bavencio), as supported by findings from JAVELIN-Bladder100, he reported.

Another factor influencing treatment selection is hepatic function, Park said. Patients with elevated liver enzymes or cirrhosis may be suboptimal candidates for enfortumab vedotin and may instead benefit from regimens such as those explored in the phase 3 CheckMate 901 (NCT03036098) or JAVELIN-Bladder100 trials, he explained. Moreover, older or frailer patients who may not tolerate the full intensity of up-front chemotherapy may benefit from a sequential administration approach, according to Park. Administering gemcitabine with either cisplatin or carboplatin initially, followed by maintenance avelumab in responders, could effectively mitigate treatment-related toxicity, he stated.