Clinical Overview of Enfortumab Vedotin in the Management of Locally Advanced or Metastatic Urothelial Carcinoma

AbstractThe treatment landscape for locally advanced or metastatic urothelial carcinoma has broadened significantly over recent years. New therapeutic options include immunotherapy with checkpoint inhibitors and targeted therapy with erdafitinib. Despite these advances, gaps remain in the selection and sequencing of optimal therapies. Treatment decisions are often influenced by several patient-specific factors such as tolerability and biomarker expression. Following progression while receiving front- and second-line therapies, there is no widely accepted standard of care for patients. Enrollment into a clinical trial is recommended in all lines of therapy for advanced disease. Antibody –drug conjugates have recently emerged as novel therapeutics allowing for targeted delivery of chemotherapeutic agents. Enfortumab vedotin, a nectin-4-targeted antibody conjugated with monomethyl auristatin E, is the first-in-class therapeutic option and has demonstrated unprecedented response rat es following progression on chemotherapy and immunotherapy for advanced disease with a tolerable safety profile. As a result, a biologics license application was submitted to the US FDA in July 2019. Ongoing clinical trials are aiming to further establish the role of enfortumab vedotin in urothelial carcinoma. In this article, we highlight the safety and efficacy of enfortumab vedotin for patients with advanced bladder cancer, ongoing clinical trials, clinical pharmacology, and pharmacokinetics.
Source: Drugs - Category: Drugs & Pharmacology Source Type: research

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Conditions:   Bladder Urothelial Carcinoma;   Stage III Bladder Cancer AJCC v8;   Stage IIIA Bladder Cancer AJCC v8;   Stage IIIB Bladder Cancer AJCC v8 Interventions:   Drug: Carboplatin;   Drug: Cisplatin;   Drug: Doxorubicin;   Drug: Doxorubicin Hydrochloride;   Biological: Durvalumab;   Drug: Fluorouracil;   Drug: Gemcitabine;   Drug: Gemcitabine Hydrochloride;   Drug: Methotrexate;   Drug: Mitomycin;  ...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
ConclusionsThe updated PURE-01 results confirm the activity of neoadjuvant pembrolizumab in MIBC. Patients with SCC and LEL features may be suitable for neoadjuvant immunotherapy trials. CPS and TMB are the key response predictors irrespective of the histological subtypes.Patient summaryIn the PURE-01 study, we have preliminarily evaluated the activity of neoadjuvant pembrolizumab in patients with predominant variant histology (VH). Of these patients, those harboring squamous-cell carcinoma or a lymphoepithelioma-like variant feature had major, although preliminary, pathological responses compared with those with other pre...
Source: European Urology - Category: Urology & Nephrology Source Type: research
Publication date: Available online 20 August 2019Source: European UrologyAuthor(s): Marko Babjuk, Maximilian Burger, Eva M. Compérat, Paolo Gontero, A. Hugh Mostafid, Joan Palou, Bas W.G. van Rhijn, Morgan Rouprêt, Shahrokh F. Shariat, Richard Sylvester, Richard Zigeuner, Otakar Capoun, Daniel Cohen, José Luis Dominguez Escrig, Virginia Hernández, Benoit Peyronnet, Thomas Seisen, Viktor SoukupAbstractContextThis overview presents the updated European Association of Urology (EAU) guidelines for non–muscle-invasive bladder cancer (NMIBC), TaT1, and carcinoma in situ (CIS).ObjectiveTo provide ...
Source: European Urology - Category: Urology & Nephrology Source Type: research
ConclusionsIn the setting of mUC, clinicians and patients should carefully consider how to balance the short-term benefit of chemotherapy against the long-term benefit of immunotherapy.Patient summaryTo determine the optimal first-line therapy for metastatic bladder cancer patients who are unfit for cisplatin, we compared carboplatin-based chemotherapy versus immunotherapy using real-world data. Survival in the 1st year of treatment was lower with immunotherapy relative to chemotherapy, but for patients surviving beyond the 1st year, immunotherapy was superior.
Source: European Urology - Category: Urology & Nephrology Source Type: research
AbstractBladder cancer tumors can be divided into two molecular subtypes referred to as luminal or basal. Each subtype may react differently to current chemotherapy or immunotherapy. Likewise, the technology required for comprehensive molecular analysis is expensive and not yet applicable for routine clinical diagnostics. Therefore, it has been suggested that the immunohistochemical expressions of only two markers, luminal (CK20+, CK5/6 –) and basal (CK5/6+, CK20–), is sufficient to identify the molecular subtypes of bladder cancer. This would represent a molecular grade that could be used in daily practice. Mo...
Source: Virchows Archiv - Category: Pathology Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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