(UroToday.com) The 2025 ASCO annual meeting featured a urothelial carcinoma oral abstract session and a presentation by Dr. Shilpa Gupta discussing an exploratory analysis of responders from the phase 3 EV-302 trial of enfortumab vedotin + pembrolizumab versus chemotherapy in previously untreated locally advanced or metastatic urothelial carcinoma.
EV-302/KEYNOTE-A39 showed significant progression free survival and overall survival benefits for patients with previously untreated locally advanced or metastatic urothelial carcinoma treated with enfortumab vedotin + pembrolizumab versus chemotherapy,1 which established enfortumab vedotin + pembrolizumab as the standard of care in this population. This exploratory analysis presented at the ASCO 2025 meeting demonstrates efficacy and safety results for responders, focusing on patients with confirmed complete response with ~2.5 years of median follow-up.
Patients were randomized 1:1 to receive enfortumab vedotin (1.25 mg/kg; Days 1 and 8) + pembrolizumab (200 mg; Day 1) or chemotherapy (gemcitabine + cisplatin/carboplatin); all every 3 weeks:
The primary endpoints were progression free survival by BICR and overall survival. Secondary endpoints included objective response rate, duration of response, and safety. An exploratory analysis evaluated outcomes in patients with confirmed complete response.
The median follow-up (data cutoff: August 8, 2024) was 29.1 months (95% CI, 28.5-29.9). There were 886 patients randomized to enfortumab vedotin + pembrolizumab (n = 442) versus chemotherapy (n = 444). The confirmed objective response rate (complete response + partial response) was 67.5% with enfortumab vedotin + pembrolizumab and 44.2% with chemotherapy, and confirmed complete responses were 30.4% and 14.5%, respectively:
Among patients with a confirmed complete response, 66.2% in the enfortumab vedotin + pembrolizumab arm and 59.4% in the chemotherapy arm had an initial partial response and later converted to a complete response. Baseline characteristics of responders were generally consistent with the ITT population:
Among patients with confirmed complete response in the enfortumab vedotin + pembrolizumab arm, 38 (28.6%) had upper tract disease and 20 (15%) had liver metastases. Among responders, the probability of maintained response at 24 months was ~50% with enfortumab + pembrolizumab (58.3% of responders in the enfortumab vedotin + pembrolizumab arm and 62.6% in the chemotherapy arm were cisplatin eligible):
Moreover, duration of response favored enfortumab vedotin + pembrolizumab versus chemotherapy, irrespective of cisplatin eligibility:
For patients with confirmed complete response, the median duration of complete response was not reached for enfortumab vedotin + pembrolizumab and 15.2 months for chemotherapy. The probability of maintained complete response at 2 years was 74.3% with enfortumab vedotin + pembrolizumab:
For patients with confirmed partial response, the median duration of response was 10.6 months for enfortumab vedotin + pembrolizumab and 5.4 months for chemotherapy. As such, the median duration of response was nearly twice as long with enfortumab vedotin + pembrolizumab versus chemotherapy:
Overall survival among responders favored the enfortumab vedotin + pembrolizumab arm (HR 0.59, 95% CI 0.44-0.79), with 76.3% of responders in the enfortumab vedotin + pembrolizumab arm alive at 2 years:
The overall survival among complete responders favored the enfortumab vedotin + pembrolizumab arm (HR 0.37, 95% CI 0.17-0.80), with 95.4% of complete responders in the enfortumab vedotin + pembrolizumab arm alive at 2 years:
In the overall population, enfortumab vedotin + pembrolizumab treatment was given for a median of 12 cycles (range: 1-54). For responders, enfortumab vedotin + pembrolizumab was longer (median 19 cycles, range: 1-54), and among complete responders enfortumab vedotin + pembrolizumab was given for a median of 30 cycles (range: 1-50). With longer treatment duration in responders, there was no worsening of safety seen with enfortumab vedotin + pembrolizumab:
Enfortumab vedotin’s safety profile for responders was generally consistent with the overall population:
Similarly, pembrolizumab’s safety profile for responders was generally consistent with the overall population:
Dose modifications due to treatment related adverse events were common among responders with longer treatment duration:
Dr. Gupta concluded her presentation discussing an exploratory analysis of responders from the phase 3 EV-302 trial with the following take-home points:
- In this exploratory analysis of the phase 3 EV-302 trial, enfortumab vedotin + pembrolizumab treatment improved survival versus chemotherapy in patients who achieved a complete response or partial response
- In the enfortumab vedotin + pembrolizumab arm, the proportion of patients achieving complete response (~60% cisplatin eligible) was twice that in the chemotherapy arm. Responses to enfortumab vedotin + pembrolizumab were durable, with a 74% probability of maintained complete response at 24 months
- Appropriate dose modifications/interruptions allowed for responders to continue treatment, with a safety profile similar to that in the overall population despite receiving more cycles of therapy
- Collectively, these data reinforce enfortumab vedotin + pembrolizumab as the standard of care for the first line treatment of locally advanced or metastatic urothelial carcinoma irrespective of baseline characteristics, including cisplatin eligibility
Presented by: Shilpa Gupta, MD, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.
Related content: EV-302 Data: High CR Rates and Long-Term Survival with EV-Pembro - Shilpa Gupta
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