Enfortumab vedotin plus pembrolizumab is more effective than platinum-based chemotherapy in metastatic urothelial carcinoma

1. In the management of adult patients with metastatic urothelial carcinoma (MUC), enfortumab vedotin plus pembrolizumab (EV/P) was well-tolerated and significantly more effective than gemcitabine plus cisplatin (G/C).

Evidence Rating Level: 2 (Good)

Recent clinical trials have demonstrated that EV/P offers greater overall survival (OS) and progression-free survival (PFS) compared with platinum-based chemotherapy in MUC. However, clinical trial populations often exclude patients with poor performance status or significant comorbidities. Observational studies are necessary to study whether the benefits of EV/P are observed in broader clinical settings. This retrospective cohort study included adults with MUC who initiated first-line systemic therapy with either EV/P or G/C. The primary outcome was OS. Of 4433 total patients, 1841 received EV/P (mean [SD] age, 70.6 [10.1] years) and 2592 received G/C (mean [SD], 67.2 [10.6] years). Patients in the EV/P were significantly older (P < .001), and racial distribution differed (EV/P vs. G/C; Black patients: 129 [6.7%] vs 139 [5.3%]; P = .04; White patients: 1445 [76.0%] vs 1614 [61.8%]; P < .001); Asian patients: 145 [7.6%] vs 326 [12.5%; P < .001). The EV/P group had a higher comorbidity burden, including more heart failure (275 [14.4%] vs 194 [7.4%]), diabetes (558 [29.2%] vs 560 [21.4%]), and overweight/obesity (548 [28.7%] vs 367 [14.0%]) (all P < .001). Patients receiving EV/P as first-line therapy had significantly lower all-cause mortality (HR, 0.70; 95% CI, 0.63-0.79), longer median OS (20 vs 11 months; P < .001), lower risk of early hospital admission (HR, 0.73; 95% CI, 0.64-0.83), and longer time to next treatment (median, 35 vs 10 months; HR, 0.49; 95% CI, 0.39-0.61). However, these patients also had higher incidences of skin rash (HR, 2.77; 95% CI, 2.24-3.42), diarrhea (HR, 1.42; 95% CI, 1.14-1.77), hyperglycemia (HR, 1.62; 95% CI, 1.21-2.16), and hypothyroidism (HR, 1.78; 95% CI, 1.27-2.48). In contrast, fatigue (HR, 0.76; 95% CI, 0.62-0.92), nausea (HR, 0.63; 95% CI, 0.49-0.80), and anemia (HR, 0.87; 95% CI, 0.78-0.99) were more common in the G/C group.

Click here to read the study in JAMA Network Open

Image: PD

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