DV plus toripalimab scores in HER2+ UC
Combining disitamab vedotin (DV) with toripalimab results in markedly better outcomes than platinum-based chemotherapy for patients with HER2-positive locally advanced or metastatic urothelial carcinoma, report the RC48-C016 trial investigators.
After a median follow-up of 18.2 months, median progression-free survival was 13.1 months for the 243 patients given the antibody–drug conjugate (ADC) plus immunotherapy combination every 2 weeks, compared with 6.5 months for the 241 given chemotherapy every 3 weeks, which was consistent across subgroups including HER2 and PD-L1 status.
The objective response rate by blinded independent review was 76.1% for the DV plus toripalimab group and 50.2% for the chemotherapy group, and the disease control rates were a respective 91.4% and 77.6%.
The impact of the ADC–immunotherapy combination carried through to overall survival (OS), which was a median of 31.5 months compared with 16.9 months in the chemotherapy group – also consistent across subgroups. The estimated 12-month OS rates were 79.5% for the DV plus toripalimab group and 62.5% for the chemotherapy group.
Moreover, presenter Jun Guo (Peking University Cancer Hospital and Institute, Beijing, China) reported that the ADC–immunotherapy combination was better tolerated than chemotherapy, with grade 3 adverse events occurring in 55.1% and 86.9%, respectively.
The most common grade 3 event in patients given DV and toripalimab was increased γ-glutamyltransferase level, in 7.4%, followed by anemia, hypoesthesia, decreased neutrophil count, increased lipase, and hypokalemia, all occurring in just over 5% of patients. Common events in the chemotherapy group were decreased levels of neutrophils (61.7%), white cells (47.7%), and platelets (45.9%), as well as anemia (45.5%).
Treatment-related adverse events resulted in treatment discontinuation in 12.3% of the DV plus toripalimab group and in 10.4% of the chemotherapy group. Events leading to discontinuation of ADC and/or immunotherapy included peripheral neuropathy (1.6%) and immune-mediated lung disease (1.6%).
The findings are published in The New England Journal of Medicine and were presented at the European Society of Clinical Oncology (ESMO) Congress 2025 in Berlin, Germany, where invited discussant Andrea Necchi (Vita-Salute San Raffaele University, Milan, Italy) praised the “outstanding data” and said it provides an additional treatment option for these patients. However, he also noted that the RC48-C016 trial addresses “the precise need of a precise geographic area,” citing the access and cost issues for enfortumab vedotin and pembrolizumab in China.
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