FDA Approval Summary: Belzutifan for Patients with Advanced Renal Cell Carcinoma.

On December 14, 2023, the U.S. FDA approved belzutifan (Welireg, Merck & Co.

False-Positive Circulating Tumor DNA Results Do Not Explain Lack of Efficacy for PARP Inhibitors in Patients With Castration-Resistant Prostate Cancer Harboring and Mutations.

False-positive ctDNA results do not explain lack of efficacy for PARPi in patients with ATMm and CHEK2m CRPC.

Advancing Clinical Trial Design for Non-Muscle Invasive Bladder Cancer.

Background: Despite recent drug development for non-muscle invasive bladder cancer (NMIBC), few therapies have been approved by the US Food and Drug Administration (FDA), and there remains an unmet clinical need. Bacillus Calmette-Guerin (BCG) supply issues underscore the importance of developing safe and effective drugs for NMIBC.

Objective: On November 18-19, 2021, the FDA held a public virtual workshop to discuss NMIBC research needs and potential trial designs for future development of effective therapies.

Cytoreductive nephrectomy in the era of immune checkpoint inhibitors: a US Food and Drug Administration pooled analysis.

Background: This pooled analysis of patient-level data from trials evaluated the clinical outcomes of patients with metastatic renal cell carcinoma with or without cytoreductive nephrectomy before a combination of immune checkpoint inhibitor and antiangiogenic therapy.

Methods: Data from 5 trials of immune checkpoint inhibitors plus antiangiogenic therapy were pooled. Only patients with stage 4 disease at initial diagnosis were included to ensure that nephrectomy was performed for cytoreductive purposes and not to previously treat an earlier stage of disease.

Efficacy of Poly(ADP-ribose) Polymerase Inhibitors by Individual Genes in Homologous Recombination Repair Gene-Mutated Metastatic Castration-Resistant Prostate Cancer: A US Food and Drug Administration Pooled Analysis.

Purpose: We performed a pooled analysis of multiple trials of poly(ADP-ribose) polymerase inhibitors (PARPi) in metastatic castration-resistant prostate cancer (mCRPC) to investigate the efficacy of PARPi in each individual homologous recombination repair (HRR) mutated (m) gene.

Patients And Methods: We pooled patient-level data from trials of PARPi in mCRPC that reported mutation status in individual HRR genes. Any HRR gene with available data across all the randomized trials of PARPi in first-line mCRPC was selected.

FDA Approval Summary: Olaparib in Combination With Abiraterone for Treatment of Patients With -Mutated Metastatic Castration-Resistant Prostate Cancer.

Purpose: This article summarizes the US Food and Drug Administration (FDA) review of the data leading to approval of olaparib plus abiraterone for the treatment of patients with deleterious or suspected deleterious -mutated (m) metastatic castration-resistant prostate cancer (mCRPC), as determined by an FDA-approved companion diagnostic test.

Patients And Methods: Approval was based on the results from PROpel, a double-blind trial that randomly assigned 796 patients with mCRPC to abiraterone plus prednisone or prednisolone with either olaparib or placebo. The primary end point was radiographic progression-free survival (rPFS) per investigator assessment.

A U.S. Food and Drug Administration-pooled Analysis of Frontline Combination Treatment Survival Benefits by Risk Groups in Metastatic Renal Cell Carcinoma.

Background: While frontline immuno-oncology/tyrosine kinase inhibitor (IO/TKI) combination therapy has established a benefit in metastatic renal cell carcinoma (mRCC), this may differ by International Metastatic RCC Database Consortium (IMDC) risk grouping. Looking at individual trials, we noted an apparently smaller magnitude of benefit for favorable-risk disease.

Objective: We aimed to assess treatment benefit by risk groupings, especially in favorable-risk, augmenting patient numbers via a pooled analysis.

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer.

On March 23, 2022, the FDA approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan, also known as 177Lu-PSMA-617) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. The recommended 177Lu-PSMA-617 dose is 7.4 gigabecquerels (GBq; 200 mCi) intravenously every 6 weeks for up to six doses, or until disease progression or unacceptable toxicity.

FDA Approval Summary: Belzutifan for von Hippel-Lindau Disease-Associated Tumors.

On August 13, 2021, the FDA approved belzutifan (WELIREG, Merck), a first-in-class hypoxia-inducible factor (HIF) inhibitor for adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery. The FDA granted approval based on the clinically meaningful effects on overall response rate (ORR) observed in patients enrolled in Study MK-6482-004. All 61 patients had VHL-associated RCC; some also had CNS hemangioblastomas and/or pNET.

Survival outcomes in older men with non-metastatic castration-resistant prostate cancer treated with androgen receptor inhibitors: a US Food and Drug Administration pooled analysis of patient-level data from three randomised trials.

Background: Little is known about the benefit-risk profile of second-generation androgen receptor inhibitors in older men with non-metastatic castration-resistant prostate cancer. We aimed to examine the efficacy and safety of second-generation androgen receptor inhibitors in men aged 80 years or older with non-metastatic castration-resistant prostate cancer.

Methods: We searched for all randomised controlled clinical trials evaluating second-generation androgen receptor inhibitors in patients with non-metastatic castration-resistant prostate cancer submitted to the US Food and Drug Administration before Aug 15, 2020, and pooled data from three trials that met the selection criteria.

Identifying Prostate Surface Antigen Patterns of Change in Patients with Metastatic Hormone Sensitive Prostate Cancer Treated with Abiraterone and Prednisone.

Background: Despite treatment with abiraterone acetate and prednisone (AA/P), most patients with metastatic hormone sensitive prostate cancer (mHSPC) will develop castration-resistant disease (metastatic castration-resistant prostate cancer [mCRPC]). The early identification of who will progress on AA/P is limited.

Objective: This study investigates the role of prostate surface antigen (PSA) kinetics as a predictor of progression in mHSPC patients treated with AA/P.

Myeloid-Derived Suppressor Cells in Nonmetastatic Urothelial Carcinoma of Bladder Is Associated With Pathologic Complete Response and Overall Survival.

Background: Myeloid-derived suppressor cells (MDSC) have immunosuppressive activity and enhance tumor progression. We hypothesized that lower blood MDSC would correlate with pathologic complete response and better outcomes in nonmetastatic urothelial carcinoma (UC).

Patients And Methods: Before cystectomy, blood MDSC were measured in whole blood (WB) and peripheral blood mononuclear cells using flow cytometry.

On the Shoulders of Giants: The Evolution of Renal Cell Carcinoma Treatment-Cytokines, Targeted Therapy, and Immunotherapy.

The treatment of advanced renal cell carcinoma (RCC) has evolved dramatically over the past 30 years, as has a better understanding of the biology of the disease, knowledge of multiple subtypes with distinct molecular abnormalities, and improved comprehension of the perturbed pathways that lead to the development and growth of RCC. This is no longer a monolithic disease, although the majority of tumors are of the clear cell subtype. However, progress is being made in other subtypes as well, as molecular profiles are better understood and as new agents show activity.

Diagnostic and therapeutic splenectomy for splenic lymphomas: analysis of the National Cancer Data Base.

Objectives: To examine the use of splenectomy, chemotherapy, and subsequent overall survival (OS) in contemporary patients with splenic lymphomas.

Methods: We analyzed records of 6450 patients with various splenic lymphomas recorded in the National Cancer Data Base (2004-2013). Survival was compared using Mantel-Byer test to account for guarantee-time bias, stratified by age, sex, comorbidities, and lymphoma stage.

HIF Inhibitors: Status of Current Clinical Development.

Purpose Of Review: In this review, the importance of the hypoxia inducible factor (HIF) pathway in tumorigenesis and cancer treatment outcomes will be discussed. The outcomes of phase II and III clinical trials of direct HIF inhibitors in the treatment of cancer will be reviewed.

Recent Findings: The HIF signaling pathway is activated by tumor-induced hypoxia or by inactivating mutations of the VHL gene.

Therapy and outcomes of primary central nervous system lymphoma in the United States: analysis of the National Cancer Database.

Although the role of radiation therapy and chemotherapy in primary central nervous system lymphoma (PCNSL) has evolved considerably over the past decade, the application of treatment modalities in the community has not been evaluated. We analyzed the use of chemotherapy, radiation therapy, and associated overall survival, among 9165 HIV-negative PCSNL cases reported to the US National Cancer Database in 2004-2013. During this time, the proportion of patients receiving chemotherapy significantly increased from 65.

Human immunodeficiency virus-associated lymphomas in the antiretroviral therapy era: Analysis of the National Cancer Data Base.

Background: Antiviral therapy has altered the prognosis of patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL), but patterns of lymphoma-directed therapy in the community are unknown.

Methods: The authors analyzed the National Cancer Data Base records of 10,769 patients who were diagnosed with HIV-associated lymphoma from 2004 through 2012. Changes in clinical characteristics and chemotherapy delivery over time were evaluated.

Small Bowel Adenocarcinoma as the Cause of Gastrointestinal Bleeding in Celiac Disease: A Rare Malignancy in a Common Disease.

Introduction. Celiac disease is associated with an increased risk of small bowel malignancies, particularly lymphoma. Its association with small bowel carcinoma is less known.

Type D personality and quality of life in patients with irritable bowel syndrome.

Background: Some studies indicate that psychological factors and extra-intestinal symptoms affect health related quality of life (HRQoL) in patients with irritable bowel syndrome (IBS) more than what bowel symptoms themselves. Type D personality characterized by global traits including negative affectivity and social inhibition has been proposed to be related to HRQoL. The aim of this study was to determine the association between type D personality and HRQoL inpatients with IBS.