Association between drug-related cutaneous adverse events and survival outcomes in patients treated with enfortumab vedotin.

AIM OF THE STUDY: The antibody-drug conjugate enfortumab vedotin (EV) received approval in patients with metastatic urothelial carcinoma (mUC). EV-related cutaneous toxicities are frequently reported, whether EV-related AEs association with survival may exist is still unknown. We aim to report the association between cutaneous toxicities and survival in patients receiving EV.

METHODS

This retrospective study enrolled patients treated with monotherapy EV from two oncology centers, followed up for at least 3-months, and data collection demographics, treatments, toxicities, and outcomes. The primary endpoint was progression-free survival (PFS) in patients experiencing cutaneous toxicities or not. Overall survival (OS) was the secondary endpoint.

RESULTS

Data from 63 patients treated with EV from July 19, 2019, to March 12, 2024, were collected. Among them, the 18 (28.6 %) patients experiencing any-grade cutaneous toxicities during EV treatment showed significantly longer median PFS (mPFS: 9.2 vs. 4.7 months, hazard ratio [HR] 0.35; p = 0.0041) and OS (mOS: not reached vs. 8.4 months, HR 0.38; p = 0.0253). The multivariate analysis showed a significant association of cutaneous toxicities with improved PFS (HR 0.40, p = 0.0319), and did not demonstrate significant association with OS even if tendency was kept (HR 0.41, p = 0.067).

CONCLUSION

These results support that patients experiencing any-grade cutaneous toxicity (skin rash) had a prolonged PFS. With the recent expansion of combined treatment using EV plus pembrolizumab in first-line in mUC patients, cutaneous toxicities need to be carefully monitored and optimized dedicated management provided, considering that cutaneous toxicity may be predictive of patient outcome.