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.

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.