Influence of best objective response to first-line treatment on survival outcomes in advanced urothelial carcinoma in the era of sequential therapy with enfortumab vedotin

Abstract

Objective

This study evaluated whether first-line treatment affects survival outcomes in patients with advanced urothelial carcinoma undergoing sequential therapy with chemotherapy, immune checkpoint inhibitors, and enfortumab vedotin.

Methods

This multicenter retrospective study included 57 patients treated at Hiroshima University Hospital and its affiliated institutions between 2009 and 2024. Patients received chemotherapy as a first-line treatment (gemcitabine plus cisplatin or carboplatin), followed by second-line immune checkpoint inhibitors (pembrolizumab or avelumab) and third-line enfortumab vedotin. Assessed outcomes included overall survival and time to treatment failure. Cox regression analysis identified prognostic factors for overall survival.

Results

Over a median follow-up of 20.5 months, median overall survival was not reached after first-line treatment. Gemcitabine with cisplatin was selected in 31.6% of cases, while gemcitabine and carboplatin was chosen in 68.4% of cases as the first-line treatment; subsequently, 66.7% received pembrolizumab, and 33.3% received avelumab in the second-line treatment. Patients who achieved a complete or partial response with the first-line treatment had significantly longer overall survivals from both first-line and enfortumab vedotin initiation than those with stable or progressive disease. In cases that achieved complete or partial responses, avelumab was more frequently selected as a second-line therapy. However, in the first-line treatment, multivariate analysis identified only stable or progressive disease as a significant predictor of worse overall survival.

Conclusion

The best response to first-line treatment predicted both overall survival from first-line initiation and outcomes following enfortumab vedotin treatment, underscoring its prognostic value in sequential therapy for patients with advanced urothelial carcinoma.