In a U.S. retrospective cohort study reported in JAMA Oncology, Chow et al found that reduced-dose vs standard upfront enfortumab vedotin-ejfv plus pembrolizumab reduced the risk of enfortumab vedotin treatment interruption in the first-line treatment of patients with advanced urothelial cancer.
Study Details
The study used data from the Flatiron Health Research Database to identify adults diagnosed with advanced urothelial cancer who started first-line enfortumab vedotin plus pembrolizumab between April 2023 (date of enfortumab vedotin FDA accelerated approval) and December 2024. Upfront enfortumab vedotin dose reduction was defined as 1.0 or 0.75 mg/kg for either of the first two doses; standard dosing was 1.25 mg/kg for both initial doses. Propensity score modeling was used to perform inverse probability of treatment weighting (IPTW)–adjusted comparisons between patients who received upfront reduced-dose vs standard-dose enfortumab vedotin.
The primary outcome measure was time to enfortumab vedotin treatment interruption—ie, time from enfortumab vedotin plus pembrolizumab initiation to first gap of at least 35 days between consecutive enfortumab vedotin doses.
Key Findings
Among 496 patients included in the analysis, 117 (23.6%) received upfront enfortumab vedotin dose reduction. The frequency of enfortumab vedotin dose reduction increased from 21.6% at first dose to 38.8% at eighth dose.
Upfront dose reduction was associated with significantly reduced risk of enfortumab vedotin treatment interruption (IPTW-adjusted hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.30–0.82, P = .007). No significant difference was observed in overall survival (adjusted HR = 1.24, 95% CI = 0.88–1.76, P = .21).
Findings were similar for time to interruption (adjusted HR = 0.49, 95% CI = 0.25–0.96, P = .04) and overall survival (adjusted HR = 1.15, 95% CI = 0.76–1.73, P = .49) among 213 patients with physiologic vulnerabilities (older age [≥ 80 years], renal dysfunction [CrCl < 30 mL/min], or poor performance status [Eastern Cooperative Oncology Group score ≥ 2]).
The investigators stated: “To the investigators’ knowledge, this is the first real-world evidence supporting upfront enfortumab vedotin dose reduction in patients with advanced urothelial cancer initiating [first-line] enfortumab vedotin plus pembrolizumab.”
Ryan D. Chow, MD, PhD, of the Hospital of the University of Pennsylvania, Perelman Center, Philadelphia, is the corresponding author for the JAMA Oncology article.
Disclosure: For full disclosures of all study authors, visit jamanetwork.com.
