Assessing Treatment Outcomes of Patients Undergoing Enfortumab Vedotin Dose Reduction in Metastatic Bladder Cancer

Enfortumab vedotin (EV) has emerged as a key treatment for metastatic bladder cancer. The treatment paradigm is to treat until unacceptable toxicity or progression, but acute and cumulative toxicity adversely impacts quality of life (QOL). We hypothesized that dose reductions may improve QOL without sacrificing efficacy. We conducted a single-center, retrospective study to assess association of EV dose reduction with treatment duration, treatment-related adverse events (TRAEs), and survival.

Patients with metastatic bladder cancer treated with EV ± pembrolizumab were divided into three groups: standard dose (1.25 mg/kg); on-treatment dose reduction (1.25 mg/kg and dose-reduced); and upfront dose reduction (started EV < 1.25 mg/kg). We evaluated the electronic medical record for data on survival, TRAEs, and number of doses received. Kaplan-Meier and Cox proportional hazards regression models were used to compare progression-free survival (PFS) and overall survival (OS) between the three groups and evaluate treatment dose (1.25 or < 1.25 mg/kg) as a time-varying covariate. TRAEs and number of doses received were examined using logistic and negative binomial regression. Regression models adjusted for age, ECOG status, concurrent pembrolizumab, histology, and site of metastasis.

A total of 152 patients comprised the groups: standard dose, n = 47; on-treatment dose reduction, n = 72; upfront dose reduction, n = 33. Upfront dose reduction, patients were significantly older (P < .001) and had worse ECOG status (P = .054). Patients receiving on-treatment dose reduction had significantly more cutaneous AEs (26.4%, P = .005) and neuropathy (34.7%, P < .001) than standard dose patients. In 4-month landmark analyses, patients receiving on-treatment dose reduction had significant improvement in PFS (HR: 0.49, P = .027) but no difference in OS (HR: 0.60, P = .106) compared to standard dose patients. Time-varying analyses showed dose-reduced EV patients had improved PFS (HR: 0.57, P = .018) and OS (HR: 0.53, P = .017) compared to standard dosing.

EV dose reduction decreases AEs while maintaining efficacy, warranting prospective evaluation.