Desquamative extravasation reaction secondary to enfortumab vedotin.
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ABSTRACT:
SUBMITTER: Pulavarty AN
PROVIDER: S-EPMC10943994 | biostudies-literature | 2024 Apr
REPOSITORIES: biostudies-literature
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Desquamative extravasation reaction secondary to enfortumab vedotin.
Pulavarty Akshay N AN Meehan Shane S Weed Jason J
JAAD case reports 20240213
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Project description:IntroductionEnfortumab vedotin is an antibody drug conjugate approved for management of pretreated locally advanced or metastatic urothelial carcinoma, which is associated with a rare risk of drug extravasation and soft tissue reactions.Case reportWe report two cases of EV extravasation with subsequent development of bullae and cellulitis.Management and outcomeThey were both treated for cellulitis and had conservative management without surgical intervention and were able to resume treatment with Enfortumab vedotin without subsequent adverse events.DiscussionWe propose that EV acts as a vesicant upon extravasation, highlight measures to prevent extravasation events, and encourage appropriate measures when dealing such as attempt of aspiration, removal of catheter, application of compresses, and thorough documentation with photographic evidence.
| S-EPMC10612376 | biostudies-literature
Project description:The treatment landscape for metastatic urothelial cancer (mUC) beyond first-line platinum-based chemotherapy has changed significantly over the last 5 years with the recent approvals of the immune checkpoint inhibitors (ICIs), fibroblast growth factor receptor (FGFR) inhibitors and most recently Enfortumab Vedotin (EV). EV is a novel antibody-drug conjugate (ADC), that delivers monomethyl auristatin E (MMAE), a microtubule-disrupting agent, inside cells harboring the cell surface nectin-4 receptor. In mUC, EV has shown encouraging response rates and received accelerated approval from the Food and Drug Administration (FDA) in December 2019 in the post-platinum and ICI setting. EV is generally well tolerated, with the main toxicities being neuropathy, skin rash, alopecia and fatigue. Notably EV can also be administered to patients with renal dysfunction, which is commonly a concern in this patient population. EV is now being tested in combination strategies and in earlier disease settings in urothelial cancers. In this review, we will discuss its mechanism of action, clinical trials leading to FDA approval as well as ongoing trials and future directions.
| S-EPMC7780177 | biostudies-literature
Project description:BackgroundPatients with advanced urothelial carcinoma have poor overall survival after platinum-containing chemotherapy and programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor treatment.MethodsWe conducted a global, open-label, phase 3 trial of enfortumab vedotin for the treatment of patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-containing chemotherapy and had had disease progression during or after treatment with a PD-1 or PD-L1 inhibitor. Patients were randomly assigned in a 1:1 ratio to receive enfortumab vedotin (at a dose of 1.25 mg per kilogram of body weight on days 1, 8, and 15 of a 28-day cycle) or investigator-chosen chemotherapy (standard docetaxel, paclitaxel, or vinflunine), administered on day 1 of a 21-day cycle. The primary end point was overall survival.ResultsA total of 608 patients underwent randomization; 301 were assigned to receive enfortumab vedotin and 307 to receive chemotherapy. As of July 15, 2020, a total of 301 deaths had occurred (134 in the enfortumab vedotin group and 167 in the chemotherapy group). At the prespecified interim analysis, the median follow-up was 11.1 months. Overall survival was longer in the enfortumab vedotin group than in the chemotherapy group (median overall survival, 12.88 vs. 8.97 months; hazard ratio for death, 0.70; 95% confidence interval [CI], 0.56 to 0.89; P = 0.001). Progression-free survival was also longer in the enfortumab vedotin group than in the chemotherapy group (median progression-free survival, 5.55 vs. 3.71 months; hazard ratio for progression or death, 0.62; 95% CI, 0.51 to 0.75; P<0.001). The incidence of treatment-related adverse events was similar in the two groups (93.9% in the enfortumab vedotin group and 91.8% in the chemotherapy group); the incidence of events of grade 3 or higher was also similar in the two groups (51.4% and 49.8%, respectively).ConclusionsEnfortumab vedotin significantly prolonged survival as compared with standard chemotherapy in patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-based treatment and a PD-1 or PD-L1 inhibitor. (Funded by Astellas Pharma US and Seagen; EV-301 ClinicalTrials.gov number, NCT03474107.).
| S-EPMC8450892 | biostudies-literature
Project description:The treatment paradigm for urothelial carcinoma (UC), a common genitourinary cancer, has significantly expanded in recent years. Enfortumab vedotin, a Nectin-4-targeted antibody-drug conjugate, was recently approved by the U.S. Food & Drug Administration for patients with advanced or metastatic UC following chemotherapy and immunotherapy. Approval of enfortumab vedotin was based on findings from the EV-201 trial, which demonstrated objective response rates of 44%. Patients treated with enfortumab vedotin should be monitored for specific toxicities, including peripheral neuropathy, rash, and hyperglycemia. In this article, the clinical implications of enfortumab vedotin for the treatment of advanced UC are reviewed.
| S-EPMC7863123 | biostudies-literature
Project description:Metastatic urothelial carcinoma (mUC) is an aggressive malignancy with a dismal prognosis. Enfortumab vedotin (EV) is an antibody-drug conjugate consisting of an antibody targeting Nectin-4. This protein is highly expressed in UC cells. After binding, monomethyl auristatin E is released into cells, causing UC cell death. EV has been approved as a single agent for pre-treated mUC, with interesting improvements in response rate and survival in a setting with limited treatment options. More recently, EV approval occurred in cisplatin-ineligible naïve mUC patients in combination with pembrolizumab. Our review aims to summarize the pharmacological properties, clinical studies, and future developments of EV in mUC.
| S-EPMC10535083 | biostudies-literature
Project description:PurposeCisplatin-based combination chemotherapy remains the standard of care for locally advanced or metastatic urothelial cancer (la/mUC); however, toxicity is substantial, responses are rarely durable, and many patients with la/mUC are ineligible. Each enfortumab vedotin and pembrolizumab have shown a survival benefit versus chemotherapy in UC, are not restricted by cisplatin eligibility, and warrant investigation as a first-line (1L) combination therapy in patients ineligible for cisplatin.MethodsIn this ongoing phase Ib/II, multicenter, open-label study, 1L cisplatin-ineligible patients with la/mUC received enfortumab vedotin 1.25 mg/kg once daily on days 1 and 8 and pembrolizumab 200 mg (day 1) intravenously once daily in 3-week cycles. The primary end point was safety. Key secondary end points included confirmed objective response rate, duration of response (DOR), and overall survival (OS).ResultsForty-five patients received enfortumab vedotin plus pembrolizumab. The most common treatment-related adverse events (TRAEs) were peripheral sensory neuropathy (55.6%), fatigue (51.1%), and alopecia (48.9%). Twenty-nine patients (64.4%) had grade 3 or higher TRAEs; the most common were increased lipase (17.8%), maculopapular rash (11.1%), and fatigue (11.1%). One death (2.2%) was classified as a TRAE. The confirmed objective response rate after a median of nine cycles was 73.3% with a complete response rate of 15.6%. The median DOR and median OS were 25.6 months and 26.1 months, respectively.ConclusionEnfortumab vedotin plus pembrolizumab showed a manageable safety profile. Most patients experienced tumor shrinkage. The median DOR and median OS exceeding 2 years in a cisplatin-ineligible patient population make this a promising combination currently under investigation in a phase III study (ClinicalTrials.gov identifier: NCT04223856).
| S-EPMC10476837 | biostudies-literature
Project description:BackgroundEnfortumab vedotin shows promise as a targeted therapy for advanced urothelial carcinoma, particularly in patients who have previously received platinum-based chemotherapy and an immune-checkpoint inhibitor. The EV-301 phase III trial demonstrated significantly improved overall survival and response rates compared to standard chemotherapy. However, more data, especially from larger real-world studies, are needed to further assess its effectiveness in Japanese patients.MethodsA total of 6007 urothelial cancer patients inducted with pembrolizumab as a second-line treatment were analyzed. Among them, 563 patients received enfortumab vedotin after pembrolizumab, while 443 patients received docetaxel or paclitaxel after pembrolizumab, and all were included in the study for efficacy as a life prolonging agent.ResultsThe enfortumab vedotin group showed a longer overall survival than the paclitaxel/docetaxel group (p = 0.013, HR: 0.71). In multivariate analysis, enfortumab vedotin induction was the independent risk factor for overall survival (p = 0.013, HR: 0.70). There were no significant differences in cancer-specific survival.ConclusionsEnfortumab vedotin prolonged the overall survival for Japanese advanced or metastatic urothelial carcinoma patients compared to paclitaxel or docetaxel after pembrolizumab treatment.
| S-EPMC10486515 | biostudies-literature
Project description:BackgroundAntibody-drug conjugates have recently been introduced as a treatment for advanced urothelial carcinoma. The EV-301 study demonstrated that enfortumab vedotin (EV) improved overall survival compared with conventional chemotherapy. To assess the cost-effectiveness of EV for the treatment of advanced urothelial carcinoma (UC) from a payer perspective in middle- and high-income countries.MethodsA decision analysis model was developed to assess the efficacy and economic viability of EV as a subsequent-line treatment following disease progression in patients with advanced urothelial carcinoma already treated with PD-1 or PD-L1 inhibitors. Clinical and utility values were obtained from the published literature and available databases. Cost data were obtained from payer perspectives in the United States, United Kingdom, and China. Quality-adjusted life-years (QALYs) were used to measure health outcomes, and incremental cost-effectiveness ratios (ICERs) used to evaluate cost-effectiveness in comparison to willingness-to-pay in the United States, United Kingdom, and China. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model.ResultsCompared with chemotherapy, EV increased the benefit by 0.16-0.17 QALYs, resulting in ICERs of $2,168,746.71, $2,164,494.38, and $1,775,576.56 per QALY in the United States, United Kingdom, and China, respectively. One-way sensitivity analysis indicated that the largest effect on outcome was the utility value for progression-free survival. Probabilistic sensitivity analysis demonstrated that the probability of EV being cost-effective was 0%.ConclusionsEV provides an additional health benefit over chemotherapy for patients with advanced urothelial carcinoma but is not cost-effective from a payer perspective in the United States, United Kingdom, or China.
| S-EPMC8796084 | biostudies-literature
Project description:AimEnfortumab vedotin is an antibody-drug conjugate (ADC) that has been approved for locally advanced or metastatic urothelial cancer, as monotherapy and in combination with pembrolizumab, and has shown significant benefit in progression-free survival and overall survival for these patients. The economic burden of enfortumab vedotin hampers widespread patient access. The aim of this study was to develop a model-informed alternative dosing regimen that results in equivalent drug exposure while reducing the costs and prevent drug spillage.MethodsPopulation pharmacokinetic modelling was used to simulate a dosing regimen leading to equivalent exposure by using the published population pharmacokinetic model in the registration reports. The alternative dosing regimen was based on weight-bands derived from the established non-linear relationship between body weight and systemic exposure, and the usage of whole vials based on fixed doses to prevent spillage. Equivalent exposure compared to the approved body weight-based dosing regimen was defined as conservative equivalent boundaries of 90-111% for the calculated geometric mean ratios (GMRs) of area under the concentration-time curve and trough concentration.ResultsA weight-band based dosing regimen for each dose level of enfortumab vedotin was developed. The GMRs for all pharmacokinetic outcomes were within the predefined equivalence boundaries. In addition, a more even exposure distribution was observed across the body weight quartiles. The average costs savings across all dose levels and per weight-band were approximately 15%.ConclusionThe proposed alternative dosing regimen shows that drug costs and spillage of enfortumab vedotin can be reduced while maintaining an equivalent and more evenly distributed exposure in treated patients.
| S-EPMC11860999 | biostudies-literature
Project description:Urothelial carcinoma is a common malignancy that affects the urinary system, with bladder cancer being the most prevalent form. Although the management of early-stage disease has seen significant improvements, the treatment of locally advanced and metastatic urothelial carcinoma remains challenging. Over the past decade, there has been an explosion in the number of therapies available for the treatment of advanced disease, with immune checkpoint inhibitors and antibody-drug conjugates leading the way. Enfortumab vedotin is an antibody-drug conjugate that targets Nectin-4, a protein that is overexpressed in urothelial carcinoma cells. In clinical trials, it has shown promising outcomes for the treatment of advanced urothelial carcinoma that has progressed after chemotherapy or immunotherapy. The US Food and Drug Administration has granted expedited approval for enfortumab vedotin in the treatment of advanced urothelial carcinoma. This review provides an overview of the current and emerging treatments for urothelial carcinoma, with a particular focus on enfortumab vedotin. We discuss the mechanisms of action, clinical efficacy, safety, and ongoing research of enfortumab vedotin, along with the current landscape of other approved therapies and promising agents in development. The aim of this review is to provide a comprehensive and up-to-date summary of the available treatment options for urothelial carcinoma, including their limitations and future prospects.
| S-EPMC10362867 | biostudies-literature