Genomic Biomarkers Associated with Enfortumab Vedotin Outcomes for Patients with Advanced Urothelial Carcinoma: Analysis of UNITE Study Data.

Enfortumab vedotin (EV) is used as monotherapy or combined with pembrolizumab in advanced urothelial carcinoma (aUC), but biomarker data associated with EV outcomes are limited. We identified 170 patients in the UNITE study who received EV monotherapy and had molecular biomarker data available. Outcomes for groups with and without a particular biomarker were compared using logistic regression (unadjusted) for the objective response rate (ORR), and a log-rank test and Cox proportional-hazard models (CPHMs) for progression-free survival (PFS) and overall survival (OS) from EV initiation.

Molecular heterogeneity in urothelial carcinoma and determinants of clinical benefit to PD-L1 blockade.

Checkpoint inhibitors targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) have revolutionized cancer therapy across many indications including urothelial carcinoma (UC). Because many patients do not benefit, a better understanding of the molecular mechanisms underlying response and resistance is needed to improve outcomes. We profiled tumors from 2,803 UC patients from four late-stage randomized clinical trials evaluating the PD-L1 inhibitor atezolizumab by RNA sequencing (RNA-seq), a targeted DNA panel, immunohistochemistry, and digital pathology.

Impact of DNA Repair Deficiency in the Evolving Treatment Landscape of Bladder Cancer.

Purpose Of Review: This review explores the current landscape of treatments which target the DNA damage response (DDR) in metastatic and muscle-invasive bladder cancer. It emphasizes recent clinical trials which integrate DDR inhibitors with standard chemotherapy and immunotherapy.

Recent Findings: Noteworthy findings include the ATLANTIS trial, which demonstrated prolonged progression-free survival (PFS) in DDR biomarker-selected patients using PARP inhibitors as maintenance after standard chemotherapy.

Enhancing immunotherapy through PD-L1 upregulation: the promising combination of anti-PD-L1 plus mTOR inhibitors.

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) pathway have transformed urothelial cancer (UC) therapy. The correlation between PD-L1 expression and ICI effectiveness is uncertain, leaving the role of PD-L1 as a predictive marker for ICI efficacy unclear. Among several ways to enhance the efficacy of ICI, trials are exploring combining ICIs with serine/threonine-protein kinase mTOR (mTOR) inhibitors in different tumor types.

Induction avelumab followed by chemoimmunotherapy and maintenance versus chemotherapy alone as first-line therapy in cis-ineligible metastatic urothelial carcinoma (INDUCOMAIN): a randomized phase II study.

Background: Platinum-based chemotherapy (ChT) has been the standard first-line treatment for metastatic urothelial carcinoma (mUC). The purpose of this study was to evaluate the use of induction avelumab followed by avelumab in combination with carboplatin-gemcitabine (carbo/gem) followed by avelumab maintenance. We tested the hypothesis that induction immunotherapy (IO) could enhance the response to ChT and prevent its detrimental effect on immune cells.

Impact of Prior Chemotherapy on Response to Second-line Pembrolizumab in Urothelial Cancer: Exploratory Analysis of the Phase 3 KEYNOTE-045 Trial.

Background And Objective: Until recently, the standard first-line treatment for advanced urothelial carcinoma (UC) was platinum-based combination chemotherapy followed by avelumab maintenance therapy for patients without progressive disease (PD). For patients with advanced UC who experience PD or recurrence, standard-of-care treatment is pembrolizumab monotherapy based on the phase 3 KEYNOTE-045 study. This post hoc analysis of the KEYNOTE-045 study evaluated the efficacy of pembrolizumab compared with chemotherapy by the best response to prior platinum-based chemotherapy.

Epacadostat plus pembrolizumab versus placebo plus pembrolizumab for advanced urothelial carcinoma: results from the randomized phase III ECHO-303/KEYNOTE-698 study.

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) levels correlate with poor outcomes in urothelial carcinoma (UC). IDO1 and programmed death-ligand 1 (PD-L1) are often co-expressed. Epacadostat is a potent and highly selective inhibitor of IDO1.

Dual mTOR1/2 Inhibitor Sapanisertib (FTH-003/TAK-228) in Combination With Weekly Paclitaxel in Patients With Previously Treated Metastatic Urothelial Carcinoma: A Phase II Open-Label Study.

Background: The PI3K/AKT/mTOR pathway is frequently altered at genomic level in metastatic urothelial carcinoma (mUC). Since mTOR is the last protein in the PI3K signaling cascade, it may have the largest impact on the pathway and has been a focus of targeted therapies. Sapanisertib (FTH-003/TAK-228) is an oral highly selective mTOR1 and mTOR2 inhibitor.

Epidemiological evolution and economic impact of the COVID-19 pandemic in the European Union and worldwide and effects of control strategies on them: An ecological study.

Objective: To evaluate the epidemiological evolution and economic impact of COVID-19 pandemic in the European Union (EU) and worldwide, and the effects of control strategies on them.

Material And Methods: We collected incidence, mortality, and gross domestic product (GDP) data between the first quarter of 2020 and of 2023. Then, we reviewed the effectiveness of the mitigation and zero-COVID control strategies.

Safety profile of pembrolizumab monotherapy based on an aggregate safety evaluation of 8937 patients.

Background: Pembrolizumab has a manageable safety profile as described in its label, which was primarily based on 2799 patients who participated in clinical trials for melanoma or non-small cell lung cancer. Here, we evaluated the safety of pembrolizumab in a broader population of patients from 31 advanced cancer clinical trials across 19 cancer types.

Methods: Safety was analyzed in patients who received at least one dose of pembrolizumab (200 mg every 3 weeks [Q3W], 10 mg/kg Q2W or Q3W, or 2 mg/kg Q3W).

Immunohistochemical markers as predictors of prognosis in multifocal prostate cancer.

The impact of tumor focality on prostate cancer (PCa) prognosis has been addressed in several studies with conflicting results. Tumor foci from multifocal (MF) PCa can show highly heterogeneous molecular features. Our aim was to analyze the protein expression of PTEN, SPOP, SLC45A3, ETV1, ERG and the "triple hit" (ERG overexpression, PTEN plus SLC45A3 loss) in unifocal (UF) and MF PCa, to evaluate their value as prognostic markers according to focality, and the role of tumor heterogeneity in MF disease.

Progress in systemic therapy for advanced-stage urothelial carcinoma.

Despite recent advances, advanced-stage urothelial carcinoma (aUC) remains incurable, with 5-year survival rates of approximately 10%. Platinum-based chemotherapy has a major role as first-line therapy for most patients with aUC. The approval of the anti-PD-L1 antibody avelumab as maintenance therapy for patients without initial disease progression on platinum-based chemotherapy is an important development that has improved the survival outcomes of patients with this disease.