Analysis of the Cisplatin-Ineligible Population in EV-302

Michiel van der Heijden, MD, PhD, of the Netherlands Cancer Institute, and colleagues are presenting a follow-up analysis of patients who were ineligible for cisplatin at randomization for the EV-302/KEYNOTE-A39 study at the 2024 American Society of Clinical Oncology Annual Meeting.

EV-302 is a phase 3, randomized, open-label, global study comparing enfortumab vedotin plus pembrolizumab (EV+P) with platinum-based chemotherapy for first-line treatment of patients with locally advanced or metastatic urothelial carcinoma (la/mUC), regardless of cisplatin eligibility. In previous readouts of this study, EV+P demonstrated a statistically significant and clinically meaningful benefit compared with platinum-based chemotherapy for progression-free survival (PFS; hazard ratio [HR], 0.45; P<.00001) and overall survival (HR, 0.47; P<.00001) in the overall patient population, reducing the risk of progression and/or death by more than 50%.

To better understand the effects of EV+P in patients who were cisplatin-ineligible at treatment randomization, Dr. van der Heijden and colleagues analyzed the treatment courses and outcomes of 408 patients, including 198 who received EV+P and 210 who received platinum-based chemotherapy. In the latter cohort, 205 received carboplatin at cycle 1.

The median PFS was 10.6 months for patients receiving EV+P and 6.1 months for those receiving platinum-based chemotherapy (HR, 0.43; 95% CI, 0.33-0.55). The median overall survival was not reached in the EV+P arm and was 12.7 months in the platinum-based chemotherapy arm (HR, 0.43; 95% CI, 0.31-0.59).

Objective response rate (ORR) for patients in the EV+P arm was 63.9%, with a 24.7% complete response (CR) rate. Median duration of response was not reached (16.3 months-not reached) in these patients. ORR for those receiving platinum-based chemotherapy was 34.9%, with a 9.1% CR rate. The median duration of response was 6.6 months (range, 5.6-10.2 months).

Researchers noted that in the EV+P arm, 62 patients remained on treatment at the data cutoff. Fifty-five patients received subsequent therapy, including cisplatin (n=10) and carboplatin (n=27) as the first subsequent therapy. In the platinum-based chemotherapy arm, all patients discontinued the study treatment at the data cutoff. Among these patients, 114 received a PD-1/L1 therapy following platinum-based chemotherapy, including maintenance avelumab (n=52), and 58 patients received a PD-1/L1 therapy as a second-line treatment.

Dr. van der Heijden and colleagues further reported that grade ≥3 treatment-related adverse events (TRAEs) occurred in 58.4% and 77.1% of patients in the EV+P and platinum-based chemotherapy arms, respectively. The most common grade ≥3 TRAEs for enfortumab vedotin were skin reactions (16.2%), peripheral neuropathy (8.1%), and hyperglycemia (4.1%), while the most common grade ≥3 treatment-emergent AEs for pembrolizumab were severe skin reaction (14.7%), hepatitis (2.0%), and pneumonitis (2.0%).

“In this patient population with historically poor prognosis, EV+P improved clinical outcomes in patients who were ineligible for cisplatin,” study authors concluded, adding that the results were consistent with the overall population. “The results of EV-302 support EV+P as a new standard of care for la/mUC, including patients who are ineligible for cisplatin.”