Dr Chow on the Benefits of Upfront Dose Reduction for Enfortumab Vedotin in Urothelial Cancer

"We believe that upfront dose reduction help patients tolerate treatment better [without] compromising the efficacy of the drug, which is really important."

Ryan D. Chow, MD, a hematology/oncology fellow at Penn Medicine, the University of Pennsylvania Health System, shared findings from a real-world retrospective cohort analysis of treatment continuity, tolerability, and survival outcomes with upfront dose reduction of enfortumab vedotin-ejfv (Padcev) when administered alongside pembrolizumab (Keytruda) to patients with urothelial cancer.

Results published in JAMA Oncology demonstrated that patients starting with a reduced enfortumab vedotin dose (n = 117) at 1 mg/kg or 0.75 mg/kg achieved a 51% reduction in the likelihood of treatment interruption (adjusted HR, 0.49; 95% CI, 0.30-0.82; P = .007) vs those who began treatment with the standard 1.25-mg dose (n = 379). Crucially, this improvement in tolerability did not appear to come at the expense of clinical benefit, as no significant difference in overall survival was observed between the standard and reduced-dose groups (adjusted HR, 1.24; 95% CI, 0.88-1.76; P = .21), Chow noted. Notably, this benefit was maintained among patients who were older and/or those deemed “physiologically vulnerable,” which included patients age 85 years or older with a creatinine clearance of less than 30 mL/min and ECOG performance status of 2 or higher.

The investigators used treatment interruption as a surrogate for toxicity, operating on the premise that dose holds are typically implemented to allow patients to recover from adverse effects. Chow emphasized that these findings suggest that upfront dose reductions may allow patients to better tolerate the treatment course, adding that approximately 1 in 4 patients in real-world practice are already being started on this upfront dose reduction strategy.

By reducing the necessity for treatment breaks, this strategy may offer a more sustainable approach to administering the combination of enfortumab vedotin and pembrolizumab without compromising its therapeutic efficacy, he concluded.