Enfortumab vedotin 20mg powder for solution for infusion vials

Background: Urothelial carcinoma (UC) is a significant clinical problem, especially in locally advanced and metastatic stages, where the prognosis remains poor despite advances in immunotherapy. Enfortumab vedotin (EV), an antibody-drug conjugate (ADC) targeting Nectin-4, extends beyond direct cytotoxicity by actively modulating the immunosuppressive tumor microenvironment (TME) in preclinical models, creating a strong rationale for combination strategies. This systematic review aimed to evaluate the clinical efficacy, safety, and hypothesized immune-modulating potential of EV in the treatment of UC, particularly in combination with immunotherapy. Materials and Methods: The review was conducted in accordance with the PRISMA 2020 guidelines. PubMed, Web of Science, and ClinicalTrials.gov databases were searched to identify interventional clinical studies published between 2020 and 2026. Studies evaluating EV used as monotherapy or in combination with immunotherapy in adult patients with UC were analyzed. ORR, PFS, OS, and the incidence of treatment-related adverse events were evaluated. Individual publications originating from the same clinical trial programs were treated as linked records and analyzed collectively. Results: The analysis was primarily based on key clinical trial programs, including EV-103, EV-301, and EV-302, along with their subgroup analyses, follow-up reports, and patient-reported outcomes. EV demonstrated significant clinical efficacy in the treatment of locally advanced UC (laUC). In the EV-301 study, EV therapy significantly prolonged overall survival compared to chemotherapy (12.88 vs. 8.97 months). In the EV-302 study, EV combination therapy with pembrolizumab showed a significant improvement in progression-free survival and overall survival compared to platinum-based chemotherapy. Conclusions: EV represents a significant therapeutic advance not only as a cytotoxic agent but as a potent immune modulator with clinical efficacy that may be enhanced by its biologically hypothesized immunomodulatory mechanisms in mUC. Its clinical development reflects a critical shift from later-line monotherapy toward earlier-line combination strategies designed to target both tumor cells and the microenvironment. Further studies are needed to better define its role in the context of alternative treatment approaches and across different stages of disease.

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Whether the reported associations between enfortumab vedotin (EV)-related toxicities and efficacy remain robust after appropriate adjustment for immortal time bias (ITB) remains unclear. We conducted a systematic review and meta-analysis to evaluate these associations while accounting for time-related bias. PubMed, Web of Science, CINAHL, and the Cochrane Library were searched from inception through November 15, 2025. Studies assessing EV-related adverse events (AEs) and clinical outcomes in advanced urothelial carcinoma (UC) were included. Studies were excluded if they included malignancies other than UC, evaluated EV in combination with other systemic therapies, did not report outcomes of interest, or lacked sufficient data for extraction. Pooled hazard ratios (HRs) were computed for overall survival (OS) and progression-free survival (PFS), and pooled odds ratios were calculated for objective response rate (ORR) and disease control rate (DCR). Risk of bias was assessed using the Newcastle-Ottawa Scale. Among 13 eligible retrospective studies, 12 were included in the meta-analysis; 10 evaluated EV-related cutaneous toxicity (5 ITB-adjusted), whereas 5 evaluated peripheral neuropathy (4 ITB-adjusted). Cutaneous toxicity was associated with improved OS; this association was attenuated in ITB-adjusted analyses, with a lower HR in unadjusted studies. Cutaneous toxicity was associated with improved PFS, ORR, and DCR, but demonstrated limited robustness for PFS. For peripheral neuropathy, improved OS was observed across 4 studies (3 ITB-adjusted). Associations with ORR and DCR were based on only 2 studies. PFS was not significantly associated; sensitivity analyses suggested limited robustness. Residual heterogeneity and variability in toxicity definitions and analytical approaches remained across studies. EV-related AEs, particularly cutaneous toxicity, were associated with favorable clinical outcomes. As evidence was limited by retrospective study designs, a small number of studies, and residual heterogeneity, these findings should be considered hypothesis-generating and require confirmation in prospective studies.

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Women have poorer survival rates in advanced, metastatic, or muscle-invasive bladder cancer (MIBC) than men. Enfortumab vedotin (EV) has changed the therapy and outcomes of MIBC and advanced bladder cancer dramatically. Therefore, the primary aim of this systematic review and meta-analysis was to evaluate sex-specific differences in disease-free (DFS), progression-free (PFS), cancer-specific survival (CSS), event-free survival (EFS), and overall survival (OS) in those patients. In October 2025, we performed a systematic literature search using MEDLINE via PubMed, Embase, and Cochrane Library. This study was prospectively registered at PROSPERO (CRD420251064260). The detailed review protocol is accessible via CRD. The systematic literature search identified 249 studies, of which 17 fulfilled the inclusion criteria. No significant sex-specific difference was observed for OS (10 studies; hazard ratio [HR] 0.88; 95% confidence interval [CI], 0.73-1.06; P = .17; I² = 32%). For PFS (8 studies), female sex was associated with a significantly better outcome (HR 0.67; 95% CI, 0.57-0.78; P < .001; I² = 0%). Because the funnel plot suggested a significant publication bias, we conducted adjustment analyses, which yielded an HR of 0.41 (95% CI, 0.24-0.57; P < .001). Only limited data were available for DFS, CSS, and EFS. Overall, the risk of bias was assessed as moderate. There is very limited evidence that women have a significantly better PFS than men during treatment with EV for bladder cancer. Further studies should incorporate explicit sex-specific analyses, eg, hormonal levels or genetic aspects, which are needed.

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