Comparison of Outcomes Between African American and European American Patients With Metastatic Clear Cell Renal Cell Carcinoma Receiving Immune Checkpoint Inhibitors.

Background And Objective: Immune checkpoint inhibitors (ICIs) and ICI/tyrosine kinase inhibitor (TKI) (ICI-based) combinations are standard first-line treatment (tx) options for patients with metastatic clear cell renal cell carcinoma (mRCC). However, only 1% of patients enrolled in trials studying these agents were Blacks.

Methods: Patients with mRCC who received front-line ICI-based tx or sunitinib after 2011 were included from the Flatiron Health electronic record-derived database.

Phase II Trial of Risk-Enabled Therapy After Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer (RETAIN 1).

Purpose: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy is the standard of care for patients with muscle-invasive bladder cancer (MIBC). Mutations in DNA damage repair genes are associated with pathologic downstaging after NAC. We hypothesized that a combination of biomarker selection and clinical staging would identify patients for cystectomy-sparing active surveillance (AS).

State of the Art: The Microbiome in Bladder Cancer.

This review assesses the current understanding of the relationship between the human microbiome and BCa. Recognizing how the microbiome affects the tumor microenvironment provides valuable insights into cancer biology, potentially uncovering interactions that could be leveraged to develop innovative therapeutic approaches. By clarifying these intricate microbial-tumor dynamics, novel targets for microbiome-based interventions can be identified, ultimately improving treatment effectiveness and patient outcomes.

Olaparib plus Abiraterone for Metastatic Castration-resistant Prostate Cancer: Pharmacokinetics Data from the PROpel Trial.

PROpel (NCT03732820) was a positive phase 3 trial that demonstrated a clinically significant improvement in radiographic progression-free survival with olaparib plus abiraterone versus placebo plus abiraterone in first-line metastatic castration-resistant prostate cancer. For a subset of PROpel patients, steady-state concentrations of olaparib, abiraterone, and Δ-abiraterone were measured in blood samples collected before and at several time points after dose administration. The pharmacokinetics (PK) for each drug and metabolite were evaluated to determine whether any clinically relevant drug-drug interactions between olaparib and abiraterone occurred.

Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma.

Background: Belzutifan, a hypoxia-inducible factor 2α inhibitor, showed clinical activity in clear-cell renal-cell carcinoma in early-phase studies.

Methods: In a phase 3, multicenter, open-label, active-controlled trial, we enrolled participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies and randomly assigned them, in a 1:1 ratio, to receive 120 mg of belzutifan or 10 mg of everolimus orally once daily until disease progression or unacceptable toxic effects occurred. The dual primary end points were progression-free survival and overall survival.

Urine Biopsy as Dynamic Biomarker to Enhance Clinical Staging of Bladder Cancer in Radical Cystectomy Candidates.

Purpose: There is significant interest in identifying complete responders to neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) to potentially avoid removal of a pathologically benign bladder. However, clinical restaging after NAC is highly inaccurate. The objective of this study was to develop a next-generation sequencing-based molecular assay using urine to enhance clinical staging of patients with bladder cancer.

Advancements in Urothelial Cancer Care: Optimizing Treatment for Your Patient.

The standard treatment paradigm for muscle invasive bladder cancer has been neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy. However, efforts are ongoing to personalize treatment by incorporating biomarkers to better guide treatment selection. In addition, bladder preservation strategies are aimed at avoiding cystectomy in well-selected patients.

Role of Gut Microbiome in Neoadjuvant Chemotherapy Response in Urothelial Carcinoma: A Multi-institutional Prospective Cohort Evaluation.

Unlabelled: Neoadjuvant chemotherapy (NAC) is linked with clinical advantages in urothelial carcinoma for patients with muscle-invasive bladder cancer (MIBC). Despite comprehensive research into the influence of tumor mutation expression profiles and clinicopathologic factors on chemotherapy response, the role of the gut microbiome (GM) in bladder cancer chemotherapy response remains poorly understood. This study examines the variance in the GM of patients with bladder cancer compared with healthy adults, and investigates GM compositional differences between patients who respond to chemotherapy versus those who exhibit residual disease.

Role of perioperative immunotherapy in localized renal cell carcinoma.

Immunotherapy has proven effective in metastatic renal cell carcinoma (RCC). The current standard of treatment in localized RCC is partial or complete nephrectomy. However, after surgery, there is a high recurrence rate and survival rates ranging from 53% to 85% depending on the stage of disease at presentation.

Muscle invasive bladder cancer: where is the field headed?

Introduction: The standard treatment for muscle-invasive bladder cancer (MIBC) is cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy or upfront radical cystectomy for cisplatin-ineligible patients. In those who are ineligible for or refuse radical cystectomy, trimodal therapy with chemoradiation is offered. However, with the success of immune checkpoint inhibitors (ICI) and antibody-drug conjugates such as enfortumab vedotin in the metastatic setting, several trials are implementing these drugs in the neoadjuvant setting for cisplatin ineligible patients.

Current Landscape of Genomic Biomarkers in Clear Cell Renal Cell Carcinoma.

Context: Dramatic gains in our understanding of the molecular biology of clear cell renal cell carcinoma (ccRCC) have created a foundation for clinical translation to improve patient care.

Objective: To review and contextualize clinically impactful data surrounding genomic biomarkers in ccRCC.

Evidence Acquisition: A systematic literature search was conducted focusing on genomic-based biomarkers with an emphasis on studies assessing clinical outcomes.

A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy.

Purpose: On the basis of preclinical evidence of epigenetic contribution to sensitivity and resistance to immune checkpoint inhibitors (ICI), we hypothesized that guadecitabine (hypomethylating agent) and atezolizumab [anti-programmed cell death ligand 1 (PD-L1)] together would potentiate a clinical response in patients with metastatic urothelial carcinoma (UC) unresponsive to initial immune checkpoint blockade therapy.

Patients And Methods: We designed a single arm phase II study (NCT03179943) with a safety run-in to identify the recommended phase II dose of the combination therapy of guadecitabine and atezolizumab. Patients with recurrent/advanced UC who had previously progressed on ICI therapy with programmed cell death protein 1 or PD-L1 targeting agents were eligible.

Role of Gut Microbiome in Neoadjuvant Chemotherapy Response in Urothelial Carcinoma: A Multi-Institutional Prospective Cohort Evaluation.

Treatment with neoadjuvant chemotherapy (NAC) in muscle invasive bladder cancer (MIBC) is associated with clinical benefit in urothelial carcinoma. While extensive research evaluating role of tumor mutational expression profiles and clinicopathologic factors into chemoresponse has been published, the role of gut microbiome (GM) in bladder cancer in chemoresponse has not been thoroughly evaluated. A working knowledge of the microbiome and its effect on all forms of cancer therapy in BC is critical.

Comparative Effectiveness of Front-Line Ipilimumab and Nivolumab or Axitinib and Pembrolizumab in Metastatic Clear Cell Renal Cell Carcinoma.

Background: Treatment of metastatic renal cell carcinoma (mRCC) is rapidly evolving with new combination therapies demonstrating improved response rates and survival. There are no head-to-head prospective trials comparing an immunotherapy doublet with an immunotherapy/tyrosine-kinase inhibitor-based combination. We compare real-world outcomes in patients treated with axitinib/pembrolizumab (axi/pembro) or ipilimumab/nivolumab (ipi/nivo).

Neoadjuvant Chemotherapy with Accelerated Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Patients with Muscle-invasive Bladder Cancer: A Retrospective Age-stratified Analysis on Safety and Efficacy.

Background: The standard of care (SOC) for muscle-invasive bladder cancer (MIBC) includes cisplatin-based combination chemotherapy in the neoadjuvant setting followed by radical cystectomy. Older patients often do not receive SOC due to perceived toxicity concerns despite guideline-directed recommendations.

Objective: To characterize the safety and efficacy of neoadjuvant accelerated methotrexate, vinblastine, adriamycin, and cisplatin (aMVAC) in MIBC patients as a function of age.

Influence of first-line chemotherapy regimen on survival outcomes of patients with advanced urothelial carcinoma who received second-line immune checkpoint inhibitors.

Background: The therapeutic landscape for advanced urothelial carcinoma (mUC) has changed significantly since studies establishing superiority of cisplatin as first-line therapy were conducted. Most patients who are eligible now receive either maintenance or second-line immune checkpoint inhibitors (ICI) and data comparing first-line platinum chemotherapy agents in this setting is limited.

Patients And Methods: The objective of this study was to determine the impact of first-line platinum chemotherapy agent on survival for patients who receive second-line ICI.

The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: A Real-World Multi-Institutional Analysis.

Purpose: The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) was challenged by the results of the CARMENA trial. Here we evaluate the role of CN in mRCC patients, including those receiving modern therapies.

Materials And Methods: We included patients with synchronous mRCC between 2011-2020 from the de-identified nationwide Flatiron Health database.

Role of immunotherapy in localized muscle invasive urothelial cancer.

The standard treatment for non-metastatic muscle-invasive bladder cancer (MIBC) is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy or trimodality therapy with chemoradiation in select patients. Pathologic complete response (pCR) to neoadjuvant chemotherapy is a reliable predictor of overall and disease-specific survival in MIBC. A pCR rate of 35-40% is attained with neoadjuvant cisplatin-based chemotherapy.