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).

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.

Multidisciplinary Educational Program to Standardize Education and Management of Immune-related Adverse Events: Review and Outcomes of a Single-institution Initiative.

Objectives: The use of immune checkpoint inhibitors (ICIs) as anticancer therapy across a variety of malignancies has led to durable efficacy in a subset of patients. However, associated side effects denoted immune-related adverse events (irAEs) have emerged and can result in substantial morbidity and mortality. Particularly early in the experience of using these agents, a lack of standardized education regarding irAEs among patients and clinical providers may have contributed to poor outcomes.

NCCN Guidelines® Insights: Kidney Cancer, Version 2.2024.

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on the systemic therapy options for patients with advanced RCC and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Kidney Cancer.

A phase 1 study of nivolumab in combination with interferon-gamma for patients with advanced solid tumors.

This phase I, dose-escalation trial evaluates the safety of combining interferon-gamma (IFN-γ) and nivolumab in patients with metastatic solid tumors. Twenty-six patients are treated in four cohorts assessing increasing doses of IFN-γ with nivolumab to evaluate the primary endpoint of safety and determine the recommended phase two dose (RP2D). Most common adverse events are low grade and associated with IFN-γ.

Bispecific PSMA antibodies and CAR-T in metastatic castration-resistant prostate cancer.

Prostate cancer is the most common cancer among men and the second leading cause of cancer-related deaths in men in the United States. The treatment paradigm for prostate cancer has evolved with the emergence of a variety of novel therapies which have improved survival; however, treatment-related toxicities are abundant and durable responses remain rare. Immune checkpoint inhibitors have shown modest activity in a small subset of patients with prostate cancer and have not had an impact on most men with advanced disease.

Flutamide With or Without PROSTVAC in Non-metastatic Castration Resistant (M0) Prostate Cancer.

Background: Before 2018, there was no standard of care for non-metastatic (M0) castration resistant prostate cancer nmCRPC. Androgen receptor antagonists (ARAs) were commonly used sequentially nmCRPC.

Methods: This was a multicenter, randomized clinical trial comparing the ARA flutamide+/-PROSTVAC, a pox viral vaccine targeting PSA that includes T-cell co-stimulatory molecules.

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.

Global Meta-analysis of Urine Microbiome: Colonization of Polycyclic Aromatic Hydrocarbon-degrading Bacteria Among Bladder Cancer Patients.

Background: The application of next-generation sequencing techniques has enabled characterization of urinary tract microbiome. Although many studies have demonstrated associations between the human microbiome and bladder cancer (BC), these have not always reported consistent results, thereby necessitating cross-study comparisons. Thus, the fundamental questions remain how we can utilize this knowledge.

Phase 1, open-label, dose-escalation study on the safety, pharmacokinetics, and preliminary efficacy of intravenous Coxsackievirus A21 (V937), with or without pembrolizumab, in patients with advanced solid tumors.

Background: Oncolytic virus V937 showed activity and safety with intratumoral administration. This phase 1 study evaluated intravenous V937±pembrolizumab in patients with advanced solid tumors.

Methods: Patients had advanced non-small cell lung cancer (NSCLC), urothelial cancer, metastatic castration-resistant prostate cancer, or melanoma in part A (V937 monotherapy), and metastatic NSCLC or urothelial cancer in part B (V937+pembrolizumab).

Platinum-Free Systemic Therapy in First-Line Metastatic Urothelial Carcinoma: Mirage or Oasis in the Platinum Desert?

Journal Journal of Clinical OncologyThe systemic treatment for metastatic urothelial carcinoma has evolved over the past decade; however, changes in the first-line setting have remained elusive and dependent on platinum-based chemotherapy regimens. Hoimes et al now present an update on the results of cohort A of the EV-103 phase Ib/II trial combining enfortumab vedotin and pembrolizumab in the first-line setting for patients with cisplatin-ineligible metastatic urothelial carcinoma. The efficacy results in this small, phase I cohort demonstrate an impressive response rate with the majority of patients deriving benefit in tumor control.

Evaluation of tumor microenvironment and biomarkers of immune checkpoint inhibitor response in metastatic renal cell carcinoma.

Background: Immunotherapy combinations including ipilimumab and nivolumab are now the standard of care for untreated metastatic renal cell carcinoma (mRCC). Biomarkers of response are lacking to predict patients who will have a favorable or unfavorable response to immunotherapy. This study aimed to use the OmniSeq transcriptome-based platform to develop biomarkers of response to immunotherapy.

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).

Adjuvant atezolizumab versus placebo for patients with renal cell carcinoma at increased risk of recurrence following resection (IMmotion010): a multicentre, randomised, double-blind, phase 3 trial.

Background: The standard of care for locoregional renal cell carcinoma is surgery, but many patients experience recurrence. The objective of the current study was to determine if adjuvant atezolizumab (vs placebo) delayed recurrence in patients with an increased risk of recurrence after resection.

Methods: IMmotion010 is a randomised, double-blind, multicentre, phase 3 trial conducted in 215 centres in 28 countries.

The past, present, and future of pT0 in bladder cancer clinical trials.

Purpose Of Review: Since the establishment of neoadjuvant chemotherapy as the standard of care for patients with muscle invasive bladder cancer, the pathologic absence of disease, denoted pT0, was found to be predictive of improved overall survival. Accordingly, it has been used in clinical trials as an optimal surrogate outcome measure, even in contemporary nonchemotherapeutic interventions. We review the role of pT0 as a catalyst for change in trial design and its suitability to facilitate more efficient and timely results.

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.

Orteronel for Metastatic Hormone-Sensitive Prostate Cancer: A Multicenter, Randomized, Open-Label Phase III Trial (SWOG-1216).

Purpose: Orteronel (TAK-700) is a nonsteroidal 17,20-lyase inhibitor suppressing androgen synthesis. We evaluated the clinical benefit of orteronel when added to androgen deprivation therapy (ADT) in patients with newly diagnosed metastatic hormone-sensitive prostate cancer.

Methods: In this open-label randomized phase III study, patients with metastatic hormone-sensitive prostate cancer were randomly assigned 1:1 to ADT with orteronel (300 mg oral twice daily; experimental arm) or ADT with bicalutamide (50 mg oral once daily; control arm).

Clinical Utility of Liquid Biopsy to Identify Genomic Heterogeneity and Secondary Cancer Diagnoses: A Case Report.

Liquid biopsy is a valuable tool in advanced and metastatic cancers for detection of genomic alterations in tumors that facilitate personalized targeted therapy approaches. Analyzing circulating tumor DNA (ctDNA) using next-generation sequencing (NGS) provides an opportunity to detect tumor genomic changes during therapy and capture inter- and intra-heterogeneity of genomically divergent cancer cell evolution. Herein, we present a patient with metastatic castration-resistant prostate cancer, with progression to soft tissues, bone, and regional lymph nodes, who was treated with abiraterone plus prednisone, with excellent prostate-specific antigen response.

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.