Combination therapy using enfortumab vedotin (Padcev) and pembrolizumab (Keytruda) has shown durable responses and meaningful survival benefits in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer. The 5-year follow-up results from the phase Ib/II EV-103 Cohort A study, presented at the European Society for Medical Oncology (ESMO) annual congress, highlight the potential of this chemo-free combination.
Long-Term Outcomes
The initial phase Ib/II trial enrolled 45 patients who received the enfortumab vedotin and pembrolizumab combination. This study established the regimen as highly active, with response rates around 70%. The latest data presented at ESMO showcased the 5-year outcomes, representing the longest follow-up for patients treated with this combination.
Jonathan Rosenberg, MD, of Memorial Sloan Kettering Cancer Center, noted that most patients discontinued treatment within the first two years per protocol. However, a significant number remained off therapy and in remission. Specifically, the duration of responses in responding patients plateaued, with 47% still in remission at 5 years. Furthermore, 38% of patients were progression-free at 5 years, and the overall survival estimate was 41.5% at 5 years, according to Kaplan-Meier methods.
Historical Context and Significance
Historically, cisplatin-ineligible metastatic urothelial cancer patients treated with gemcitabine and carboplatin in the EORTC trial had a median survival of about 9 months. More contemporary trials showed outcomes of 12 to 14 months. The median overall survival exceeding two years in the EV-103 cohort, with most patients alive at two years still alive at five years, marks a significant improvement.
"This really is unprecedented," Rosenberg stated. "We haven't seen results like this in advanced urothelial cancer previously."
Future Directions
While the results from EV-103 cohort K and the long-term outcomes from EV-302 are anticipated, the current data suggest the possibility of curing a subset of patients with advanced urothelial cancer who were previously considered incurable. Historically, 3-10% of patients would be expected to survive to 5 years; the new data indicates that this number could be significantly higher.
The findings are considered "very provocative and exciting," and further long-term data will be closely monitored.
