2015P - Serum nectin-4: Prognostic and predictive value in bladder cancer?

Background

Antibody drug conjugate (ADC) therapy using enfortumab-vedotin (EV) that targets nectin-4 increased progression-free as well as overall survival of patients with metastatic bladder cancer (BC) dramatically. However, the expression of nectin-4 on the tumor cells is not in all patients sufficient for an effective therapy with EV. In addition, the expression on metastases as the target lesions is even lower and often differed compared to primary tumors. Therefore, analysis of nectin-4 in blood from patients could be helpful to select patients for EV therapy and to monitor therapy response. The aim of this study was to analyze the diagnostic, prognostic and predictive value of nectin-4 in serum of BC patients.

Methods

Serum samples from 92 patients with BC (pTa=22, pT1=18, pT2=18, pT3=21, pT4=13) were obtained before surgery or before and during EV monotherapy or EV combination therapy with pembrolizumab (n=10). Nectin-4 was quantified by using an ELISA kit (Abcam, Germany). Statistical analysis was performed to test possible correlations with histopathological parameters using Mann-Whitney-U test or Kruskal-Wallis test. In addition, nectin-4-was quantified at different time points in patients who received EV therapy in first, second or third line settings.

Results

Nectin-4 concentration is significantly associated with T-category (p=0.0073) and increased with increasing T-category. Patients with lymph node metastases (pN+) at time of surgery exhibited significantly higher nectin-4 concentrations compared to those without metastases (pN-) (p=0.004). A trend of higher concentrations was observed in higher grades. Nectin-4 was detected in all metastatic patients before EV therapy and rose continuously during therapy in most cases. Correlation analysis with response will be presented at the congress as re-staging is currently ongoing.

Conclusions

To our knowledge, this is the first report on detection of nectin-4 in serum from patients with bladder cancer. Invasiveness and metastasis are associated with increased serum nectin-4 concentrations. nectin-4 in serum and the dynamic changes during therapy could be useful markers for therapy optimization. However, its predictive value has to be evaluated in larger studies considering mono- and combination therapies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.