RW data support enfortumab vedotin-pembrolizumab combo as 1L Tx for bladder cancer

Real-world (RW) data presented at ASCO GU 2026 support the use of enfortumab vedotin plus pembrolizumab (EV+P) as frontline treatment for advanced urothelial carcinoma (UC).

In a retrospective study, investigators identified patients with advanced or metastatic UC receiving first-line (1L) EV+P or gemcitabine-platinum (GP) chemotherapy from the TriNetX Global Health Research Network. Using propensity-score matching, participants were matched based on age, sex, race, ECOG PS, comorbidities, and baseline laboratory data. Each cohort comprised 836 participants. The median follow-up was 203 days for EV+P and 460 days for GP. [ASCO GU 2026, abstract 706]

Compared with GP, EV+P was associated with a significantly lower incidence of all-cause mortality (26.8 percent vs 47.7 percent; risk ratio [RR], 0.561; p<0.0001) and a higher survival probability at 2 years (52.6 percent vs 44 percent; log-rank p=0.0339).

Hospitalization rate was slightly lower in the experimental vs the GP arm (44.5 percent vs 49.2 percent; RR, 0.905; p=0.056).

The EV+P arm also had significantly lower incidences of grade ≥3 anaemia (20.9 percent vs 50.7 percent), thrombocytopenia (2.2 percent vs 30 percent), and neutropenia (6.1 percent vs 27.8 percent; p<0.0001 for all) than the GP arm. Conversely, the former had higher rates of rash (26 percent vs 9 percent), pruritus (18 percent vs 5 percent), and peripheral neuropathy (16 percent vs 7 percent) than the latter.

A histologic subtype analysis revealed a consistently longer median survival (626–719 vs 539–568 days) and higher survival probabilities (47.6–48.4 percent vs 40.8–44.3 percent) with EV+P than with GP across UC types*. According to the investigators, these results underpin the superior efficacy of EV+P in these aggressive variants.

“In this global, RW cohort with a 2-year follow-up, EV+P demonstrated significantly improved survival and reduced haematologic toxicity compared with GP chemo in the 1L treatment of advanced UC,” said the researchers.

“Although EV+P was associated with more skin and neurologic adverse events (AEs), these results support the use of EV+P as a preferred frontline treatment option in eligible patients,” they added.

Supporting data

Another study using TriNetX data included adults with stage IV metastatic UC treated between 2019 and 2025. Cohorts were defined by index therapy with EV+P or GP. Propensity-score matching yielded 325 patients in each arm (mean age 70 years, 75 percent men). [ASCO GU 2026, abstract 778]

EV+P also trumped GP in terms of overall survival (OS) at both 12 (72.5 percent vs 62.8 percent; hazard ratio [HR], 0.70; p=0.017) and 24 months (57.1 percent vs 48.2 percent; HR, 0.70; p=0.010).

Time to next treatment was markedly longer with EV+P than with GP (HR, 0.08; p<0.001). Of note, only 64 EV+P recipients initiated subsequent therapy within 24 months. “This result indicates durable disease control,” the researchers said.

Laboratory analyses showed no clinically meaningful differences in renal function or albumin between treatment arms, but haemoglobin level was higher with EV+P than with GP (p<0.0001).

The risk of treatment-related AE proxies (neuropathy, dermatitis, or pruritus) was higher with EV+ P vs GP (45.1 percent vs 27.8 percent; HR, 2.71; p<0.001). According to the researchers, this underscores the importance of proactive toxicity management.

Inpatient/emergency department (ED) visits were less frequent with EV+P vs GP at both 6 (58.2 percent vs 71.1 percent; HR, 0.76; p=0.001) and 12 months (65.8 percent vs 78.2 percent; HR, 0.67; p=0.008). “The lower healthcare utilization suggests improved outpatient disease control,” they said.

The EV-302 randomized trial has shown the superiority of EV+P over platinum-based chemotherapy. [N Engl J Med 2024;390:875-888] “However, RW populations often differ from clinical trial cohorts with respect to age, comorbidity burden, and treatment patterns,” the investigators noted.

“RW comparative effectiveness data are needed to validate survival benefit, treatment durability, toxicity proxies, and healthcare utilization in routine clinical practice,” they said.

Despite the higher incidences of dermatologic and neuropathic AE proxies, this RW study shows superior survival and treatment durability with 1L EV+P than with GP, they noted.

“These findings align with randomized trial data and extend their generalizability to routine clinical practice. RW durability benefits may explain the reduction in inpatient and ED encounters,” the researchers added. “These results support EV+P as a highly effective 1L regimen for metastatic UC outside of clinical trials.”