Can disitamab vedotin be used to treat HER2-negative urothelial carcinoma patients?
Disitamab vedotin (DV) is an antibody-drug conjugate that targets HER2. While it was initially developed for HER2-positive cancers, recent studies have tested it in patients with HER2-negative (IHC 0) and HER2-low (IHC 1+) urothelial carcinoma. The evidence suggests DV can provide benefit even in HER2-negative cases, though the response rate is modest compared to HER2-low patients.
What the research says
A systematic review and meta-analysis of 16 studies including 279 patients with HER2-negative or HER2-low advanced urothelial carcinoma found that DV-based therapy achieved an overall objective response rate (ORR) of 51% and a disease control rate (DCR) of 75% 36. However, when broken down by HER2 status, the ORR was 34% in HER2-negative patients versus 55% in HER2-low patients 36. Median progression-free survival was about 5.5 months overall 36.
A phase 2 trial specifically enrolled 19 patients with HER2-negative (IHC 0) or HER2-low (IHC 1+) metastatic urothelial carcinoma who had received prior chemotherapy. The confirmed ORR was 31.6%, and the disease control rate was 94.7% 7. Median progression-free survival was 5.5 months, and median overall survival was 16.4 months 7.
Real-world data from a multicenter retrospective study of 38 patients, including those with HER2-negative status, showed that DV alone or combined with a PD-1 inhibitor produced an ORR of 63.2% and a DCR of 89.5% 8. Another real-world study of 132 patients receiving DV plus a PD-1 inhibitor also reported high response rates, though specific HER2-negative subgroup results were not detailed 4.
Overall, DV has activity in HER2-negative urothelial carcinoma, but the response is lower than in HER2-low disease. The evidence is based on relatively small numbers of HER2-negative patients, so results should be interpreted with caution.
What to ask your doctor
- What is my exact HER2 status (IHC 0 vs 1+ vs 2+ with FISH)?
- Would disitamab vedotin be a reasonable option for me given my HER2-negative result?
- What are the expected response rates and side effects of DV in HER2-negative disease?
- Should I consider combining DV with a PD-1 inhibitor, and is that available for my situation?
- Are there clinical trials testing newer treatments for HER2-negative urothelial carcinoma?
This question is drawn from common patient questions about this topic and answered using cited medical research. We do not provide individualized advice.