A recent retrospective analysis suggests that enfortumab vedotin (Padcev) demonstrates a manageable safety profile in ultra-elderly patients with urothelial carcinoma, though researchers note the study's limitations in sample size and design.
The findings, presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium, examined data from 26 patients aged 80 years and older treated at two Southern California academic institutions between December 2019 and September 2024.
Patient Demographics and Treatment Details
The study population had a median age of 86.5 years (range: 80-97), with 83.6% being male. The ethnic distribution included 53.8% Caucasian, 23.1% Asian, 15.4% Hispanic, and 7.7% other. Researchers categorized patients into three age groups: 80-84 years (38.5%), 85-89 years (46.2%), and 90+ years (15.4%).
Most patients (69.2%) received enfortumab vedotin monotherapy, while 30.8% received combination therapy with pembrolizumab (Keytruda). Among monotherapy patients, 88.9% had previous exposure to PD-1/PD-L1 inhibitors.
Dosing Patterns and Safety Findings
The study revealed distinct dosing patterns across age groups. In the 80-84 age group, 70% started at 1.0 mg/kg, while the 85-89 age group showed more conservative dosing, with 41.7% starting at 0.75 mg/kg. The 90+ age group had varied initial dosing, with 50% receiving 1.0 mg/kg.
Treatment-related adverse events (TRAEs) showed correlation with dosing levels:
- Higher doses (1.0 mg/kg) had the most TRAEs (46.2%)
- Lower doses demonstrated fewer adverse events
- No grade 4/5 toxicities were observed
- Most common toxicities were grade 1 (30.8%)
Common adverse events included:
- Neuropathy (34.6%)
- Ocular symptoms (19.2%)
- Pruritus, rash, abnormal electrolytes, and fatigue (15.4% each)
- Nausea and diarrhea (3.8% each)
Treatment Modifications and Duration
The study revealed that 50% of patients required at least one dose reduction, while 42.3% experienced dose delays. Treatment discontinuation due to TRAEs occurred in 30.8% of patients. At data cutoff, 27% of patients remained on treatment, with a median of 10.5 infusions over approximately 19.5 weeks.
Clinical Context
Enfortumab vedotin received FDA approval as monotherapy for advanced urothelial cancer in July 2021, with the combination therapy with pembrolizumab gaining full approval in December 2023. The EV-302 study previously reported grade 3 or higher TRAEs in 55.9% of patients, with a 35% discontinuation rate in the combination therapy group.
The researchers concluded that upfront dose reduction may be an effective strategy for managing TRAE risk in ultra-elderly patients, though they emphasized the need for larger prospective studies to confirm these findings.
