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Results also show that reducing the Padcev dose at treatment initiation may benefit older patients with urothelial carcinoma, a type of bladder cancer.
Padcev may be safe for older patients with urothelial carcinoma, with reduced starting doses leading to fewer side effects.
Treatment with Padcev (enfortumab vedotin) for urothelial carcinoma, a type of bladder cancer, may not cause excessive or unexpected side effects particularly in patients aged 80 years and older, recent study findings suggest.
Of note, results from this study, which were presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium, were from a small patient population and based on an assessment of patients after they were treated.
More patients aged 85 years and older received upfront Padcev dose reduction. There were fewer grade 2/3 (moderate to severe) treatment-related side effects with lower starting doses of Padcev.
“Up-front dose reduction of [Padcev] may be a good strategy to mitigate [treatment-related side effect] risk,” the researchers wrote in the abstract.
Ocular symptoms: related to the eyes or vision.
Neuropathy: damage to the nerves or the peripheral nervous system, causing pain, numbness, muscle weakness, tingling and loss of sensation.
Pruritus: itching.
Abnormal electrolytes: an imbalance of substances such as sodium, potassium, chloride, magnesium, calcium and phosphate. This can be caused by dehydration or overhydration, hormonal imbalances, kidney disease, medications or other factors.
The median age of the 26 patients included in this study was 86.5 years. The patients were categorized by age: group 1 were aged 80 to 84 years (38.5%), group 2 were aged 85 to 89 years (46.2%) and group 3 were aged 90 years and older (15.4%). Regarding treatment, 69.2% of patients were treated with Padcev monotherapy and 30.8% were treated with Padcev plus Keytruda (pembrolizumab). Nearly all patients treated with Padcev monotherapy — 88.9% — previously received a PD-1/PD-L1 inhibitor.
At data cutoff, 27% of patients were still treated with Padcev, with a median number of Padcev infusions of 10.5 and a median number of weeks on the treatment of 19.5.
The majority of patients in group 1 received an Padcev starting dose of 1 mg/kg (70%) compared with 1.25 mg/kg (30%). In group 2, most patients received a starting dose of 0.75 mg/kg (41.7%), followed by 1 mg/kg (25%), 1.25 mg/kg (16.7%) and 0.5 mg/kg (16.7%). Half of the patients in group 3 received a starting dose of 1 mg/kg (50%), followed by 1.25 mg/kg (25%) then 0.5 mg/kg (25%).
After starting treatment with Padcev, 50% of patients had at least one dose reduction, 42.3% had at least one delayed dose and 30.8% had discontinued Padcev due to treatment-related side effects.
For toxicity, the most common severity was grade 1 (mild; 30.8%), followed by grade 0 (no side effects occurred; 26.9%), grade 2 (26.9%) and grade 3 (15.4%). No patients in the study experienced grade 4/5 (life-threatening or causing death) toxicities.
When assessed by starting dose, the percentage of patients with treatment-related side effects related to Padcev was highest in those who received 1 mg/kg (46.2%), followed by 1.25 mg/kg (23.1%), 0.75 mg/kg (19.2%) and 0.5 mg/kg (11.5%).
Some of the specific treatment-related side effects that occurred in the study include ocular symptoms (19.2%), neuropathy (34.6%) and nausea/diarrhea (3.8% each). Additionally, pruritus, rash, abnormal electrolytes and fatigue occurred at a rate of 15.4% each.
In this analysis, researchers reviewed data from patients with urothelial carcinoma who were treated with either Padcev monotherapy or Padcev plus Keytruda. Patients were aged 80 years or older when starting treatment with Padcev and had to receive at least one dose of Padcev.
The antibody drug conjugate Padcev was approved by the FDA in July 2021 as monotherapy for locally advanced or metastatic urothelial cancer. The combination of Padcev and Keytruda was granted accelerated approval by the FDA in April 2023 for locally advanced or metastatic urothelial cancer. This was converted to a full approval in December 2023.
Within the background section of the abstract, researchers noted that Padcev was associated with several toxicities, “which are mostly nonoverlapping with those of [Keytruda],” they wrote.
Based on findings from the EV-302 study, previously published in The New England Journal of Medicine, 55.9% of patients experienced grade 3 or higher treatment-related side effects. Treatment discontinuation occurred in 35% of patients receiving Padcev plus Keytruda.
“[Patients] aged 80 years or older (i.e., the ultra-elderly) are a special population who may be particularly vulnerable to [Padcev] toxicity,” the researchers wrote in the abstract.
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