Baseline Disease Characteristics and Platinum Sensitivity as Predictors of Outcomes in Sequential Therapy with Platinum-Based Chemotherapy, Avelumab Maintenance, and Enfortumab Vedotin in Advanced Urothelial Carcinoma (ARON-2EV Study).

BACKGROUND

Numerous case series have corroborated the efficacy of the first-line approach of platinum-based chemotherapy and avelumab maintenance followed by enfortumab vedotin monotherapy (PBC-AM-EV) in real-world patients with advanced urothelial carcinoma.

OBJECTIVE

The present investigation aimed to characterize the baseline clinical and pathological characteristics and outcomes of the PBC-AM-EV treatment sequence in the advanced urothelial carcinoma population.

METHODS

ARON-2EV is a global retrospective study investigating the real-world use of EV in patients with advanced urothelial carcinoma. Two hundred and three patients receiving PBC-AM-EV were analyzed. Primary endpoints were disease response, therapy sequence duration, and overall survival. Secondary objectives included the evaluation of clinical factors associated with outcomes. Patient characteristics were analyzed using descriptive statistics; overall survival and therapy sequence duration were estimated using the Kaplan-Meier method and assessed with log-rank tests and Cox proportional hazards models.

RESULTS

Following a median follow-up of 23.1 months, the median overall survival from PBC initiation was 31.6 months, with a 2-year overall survival rate of 68%. Survival outcomes were consistent across most clinicopathologic subgroups, but were significantly influenced by Eastern Cooperative Oncology Group performance status, prior response to PBC, and cisplatin-based regimens. Median therapy sequence duration was 26.5 months and was prolonged in patients with exclusive nodal metastases and cisplatin exposure. A 43% objective response rate was achieved by EV, including durable disease control, particularly among patients who benefited from prior PBC and avelumab maintenance.

CONCLUSIONS

The PBC-AM-EV sequence demonstrates sustained real-world efficacy, with outcomes driven by baseline characteristics, platinum responsiveness, and preserved EV activity irrespective of prior immunotherapy response.