Subgroup Analyses Offer New Understandings of EV, Pembrolizumab Benefit in la/mUC

A late-breaking abstract at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium shows improved outcomes in patients with previously untreated locally advanced metastatic urothelial carcinoma (la/mUC) after enfortumab vedotin (EV) plus pembrolizumab compared with chemotherapy, even in patient subgroups with historically poor prognosis.

EV-302/KEYNOTE-A39 originally showed that EV plus pembrolizumab leads to 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 (OS; HR, 0.47; P<.00001) in the overall patient population.

Among the 886 total patients, PFS and OS were prolonged for those receiving EV plus pembrolizumab in prespecified subgroups, including race, cisplatin eligibility, PD-L1 expression, metastatic site, liver involvement, and renal function.

Michiel Simon Van der Heijden, MD, PhD, and colleagues performed subgroup analyses to determine the OS benefit of EV plus pembrolizumab versus chemotherapy across baseline patient and disease characteristics not previously reported. Results showed:

• Race, White: 26.1 versus 15.3 months, respectively (HR, 0.47; 95% CI, 0.36-0.60)
• Race, other: not reached versus 19.3 months, respectively (HR, 0.46; 95% CI, 0.29-0.72)
• Metastatic disease site, visceral metastases: 25.6 versus 13.6 months, respectively (HR, 0.47; 95% CI, 0.37-0.60)
• Metastatic disease site, lymph node only: not reached versus 27.5 months, respectively (HR, 0.46; 95% CI, 0.27-0.78)
• Renal function, normal: 26.1 versus 18.4 months, respectively (HR, 0.51; 95% CI, 0.30-0.86)
• Renal function, mild: not reached versus 16.4 months, respectively (HR, 0.44; 95% CI, 0.30-0.65)
• Renal function, moderate/severe: 31.5 versus 13.3 months, respectively (HR, 0.50; 95% CI, 0.37-0.69)

“OS benefit was consistently observed across select prespecified subgroups, including those historically associated with poor prognosis,” Dr. Van der Heijden and colleagues concluded. “The results of these subgroup analyses support the findings of the primary analysis, which indicate that EV plus pembrolizumab is a potential new standard of care for first-line la/mUC.”