Enfortumab Vedotin在先前治疗的晚期尿路上皮癌中的作用

background

Patients with advanced urothelial carcinoma have poor overall survival after treatment with platinum-based chemotherapy and programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors.

method

We conducted a global, open-label, phase 3 trial of enfortumab vedotin in patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-containing chemotherapy and had disease progression during or after treatment with a PD-1 or PD-L1 inhibitor. Patients were randomly assigned in a 1:1 ratio to receive enfortumab vedotin (at a dose of 1.25 mg/kg of body weight on days 1, 8, and 15 of a 28-day cycle) on day 1 of a 21-day cycle or investigator's choice of chemotherapy (standard docetaxel, paclitaxel, or vinflunine). The primary endpoint was overall survival.

result

A total of 608 patients underwent randomization; 301 patients were assigned to receive enfortumab vedotin and 307 patients were assigned to receive chemotherapy.

As of July 15, 2020, a total of 301 deaths had occurred (134 in the enfortumab vedotin group and 167 in the chemotherapy group).

At the time of the prespecified interim analysis, the median follow-up was 11.1 months. The overall survival of the enfortumab vedotin group was longer than that of the chemotherapy group (median overall survival: 12.88 months vs. 8.97 months). The progression-free survival in the enfortumab vedotin group was also longer than that in the chemotherapy group (median progression-free survival: 5.55 vs. 3.71 months).

The incidence of treatment-related adverse events was similar in the two groups (93.9% in the enfortumab vedotin group and 91.8% in the chemotherapy group); the incidence of grade ≥3 events was also similar in both groups (51.4% and 49.8%, respectively).

Conclusion

Enfortumab vedotin significantly extended survival compared with standard chemotherapy in patients with locally advanced or metastatic urothelial cancer who had received prior platinum-containing therapy and a PD-1 or PD-L1 inhibitor.