EV-302: Nectin-4 Expression and Response to First-Line EV/Pembro

Enfortumab vedotin plus pembrolizumab (EV/pembro) may offer first-line progression-free survival (PFS) and overall survival (OS) benefit in patients with locally advanced or metastatic urothelial carcinoma (la/mUC), regardless of Nectin-4 expression, according to the latest EV-302 data readout.

Nectin-4 likely does not predict benefit from EV/pembro, according to the data readout at the European Society for Medical Oncology Congress 2024.

Thomas Powles, MBBS, MRCP, MD, and colleagues previously demonstrated the PFS and OS benefit of EV/pembro versus platinum-based chemotherapy in patients with la/mUC, regardless of PD-L1 expression. In the EV-302 study, patients with previously untreated disease were randomized (1:1) to EV (1.25 mg/kg IV; days 1 and 8, every 3 weeks) and pembro (200 mg IV; day 1, every 3 weeks) or chemotherapy (gemcitabine plus cisplatin/carboplatin).

Baseline Nectin-4 expression was retrospectively assessed by immunohistochemistry in tumor tissue. Expression was evaluable in 800 of the 886 randomized patients; 394 in the EV/pembro arm and 406 in the chemotherapy arm.

H-scores of 150 and 225 represent 50% and 75%, respectively, of the H-score range (0-300) and were used for subgroup analyses (<150, ≥150 to <225, and ≥225). Researchers assessed PFS and OS in Nectin-4 expression subgroups. Nectin-4 expression was assessed in responders and non-responders.

Dr. Powles and colleagues found that Nectin-4 H-scores skewed toward high expression, which was consistent with previous reports in the la/mUC population. The median H-score was 280 and 270 in the EV/pembro and chemotherapy arms, respectively. Researchers noted that 38 and 50 patients, respectively, had an H-score of less than 150.

In the H-score subgroups, the hazard ratios (95% CI) for EV/pembro versus chemotherapy for PFS were 0.40, 0.68, and 0.54, respectively. For OS, the hazard ratios were 0.47, 0.44, and 0.53, respectively.

Furthermore, researchers added that the median H-scores for treatment responders and non-responders were 284.5 and 270, respectively, in the EV/pembro arm versus 280 and 265, respectively, in the chemotherapy arm.

“EV/pembro showed consistent PFS and OS benefit across subgroups regardless of Nectin-4 expression,” the researchers concluded, adding that Nectin-4 does not predict EV/pembro benefit.